Pub Date : 2024-09-18DOI: 10.3389/fimmu.2024.1373766
Takaharu Sasaki, Yuna Ota, Yui Takikawa, Tommy Terrooatea, Takashi Kanaya, Masumi Takahashi, Naoko Taguchi-Atarashi, Naoko Tachibana, Haruka Yabukami, Charles D. Surh, Aki Minoda, Kwang Soon Kim, Hiroshi Ohno
Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using Apcmin/+ mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer’s patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens. On the follicle-associated epithelium (FAE) of PPs, microfold (M) cells pass food antigens from lumen to the dendritic cells to induce T cells. Single-cell RNA-seq (scRNA-seq) analysis of immune cells in PPs revealed a significant impact of food antigens on the induction of the PP T cells and the antigen presentation capacity of dendritic cells. These data demonstrate the role of food antigens in the suppression of small intestinal tumorigenesis by PP-mediated immune cell induction.
{"title":"Food antigens suppress small intestinal tumorigenesis","authors":"Takaharu Sasaki, Yuna Ota, Yui Takikawa, Tommy Terrooatea, Takashi Kanaya, Masumi Takahashi, Naoko Taguchi-Atarashi, Naoko Tachibana, Haruka Yabukami, Charles D. Surh, Aki Minoda, Kwang Soon Kim, Hiroshi Ohno","doi":"10.3389/fimmu.2024.1373766","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1373766","url":null,"abstract":"Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using <jats:italic>Apc<jats:sup>min/+</jats:sup></jats:italic> mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer’s patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens. On the follicle-associated epithelium (FAE) of PPs, microfold (M) cells pass food antigens from lumen to the dendritic cells to induce T cells. Single-cell RNA-seq (scRNA-seq) analysis of immune cells in PPs revealed a significant impact of food antigens on the induction of the PP T cells and the antigen presentation capacity of dendritic cells. These data demonstrate the role of food antigens in the suppression of small intestinal tumorigenesis by PP-mediated immune cell induction.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.3389/fimmu.2024.1457690
Yun Hoo Park, Sung Won Lee, Tae-Cheol Kim, Hyun Jung Park, Luc Van Kaer, Seokmann Hong
Introductionα-galactosylceramide (α-GalCer), a prototypical agonist of invariant natural killer T (iNKT) cells, stimulates iNKT cells to produce various cytokines such as IFNγ and IL4. Moreover, repeated α-GalCer treatment can cause protective or pathogenic outcomes in various immune-mediated diseases. However, the precise role of α-GalCer-activated iNKT cells in sepsis development remains unclear. To address this issue, we employed a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced murine sepsis model and two alternative models.MethodsSepsis was induced in wild-type (WT) C57BL/6 (B6) mice by three methods (LPS/D-GalN, α-GalCer/D-GalN, and cecal slurry), and these mice were monitored for survival rates. WT B6 mice were intraperitoneally injected with α-GalCer or OCH (an IL4-biased α-GalCer analog) one week prior to the induction of sepsis. To investigate the effects of α-GalCer-mediated iNKT cell activation on sepsis development, immune responses were analyzed by flow cytometry using splenocytes and liver-infiltrating leukocytes. In addition, a STAT6 inhibitor (AS1517499) and an IL10 inhibitor (AS101) were employed to evaluate the involvement of IL4 or IL10 signaling. Furthermore, we performed B cell adoptive transfers to examine the contribution of α-GalCer-induced regulatory B (Breg) cell populations in sepsis protection.ResultsIn vivo α-GalCer pretreatment polarized iNKT cells towards IL4- and IL10-producing phenotypes, significantly attenuating LPS/D-GalN-induced septic lethality in WT B6 mice. Furthermore, α-GalCer pretreatment reduced the infiltration of immune cells to the liver and attenuated pro-inflammatory cytokine production. Treatment with a STAT6 inhibitor was unable to modulate disease progression, indicating that IL4 signaling did not significantly affect iNKT cell-mediated protection against sepsis. This finding was confirmed by pretreatment with OCH, which did not alter sepsis outcomes. However, interestingly, prophylactic effects of α-GalCer on sepsis were significantly suppressed by treatment with an IL10 antagonist, suggesting induction of IL10-dependent anti-inflammatory responses. In addition to IL10-producing iNKT cells, IL10-producing B cell populations were significantly increased after α-GalCer pretreatment.ConclusionOverall, our results identify α-GalCer-mediated induction of IL10 by iNKT and B cells as a promising option for controlling the pathogenesis of postoperative sepsis.
{"title":"The iNKT cell ligand α-GalCer prevents murine septic shock by inducing IL10-producing iNKT and B cells","authors":"Yun Hoo Park, Sung Won Lee, Tae-Cheol Kim, Hyun Jung Park, Luc Van Kaer, Seokmann Hong","doi":"10.3389/fimmu.2024.1457690","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1457690","url":null,"abstract":"Introductionα-galactosylceramide (α-GalCer), a prototypical agonist of invariant natural killer T (iNKT) cells, stimulates iNKT cells to produce various cytokines such as IFNγ and IL4. Moreover, repeated α-GalCer treatment can cause protective or pathogenic outcomes in various immune-mediated diseases. However, the precise role of α-GalCer-activated iNKT cells in sepsis development remains unclear. To address this issue, we employed a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced murine sepsis model and two alternative models.MethodsSepsis was induced in wild-type (WT) C57BL/6 (B6) mice by three methods (LPS/D-GalN, α-GalCer/D-GalN, and cecal slurry), and these mice were monitored for survival rates. WT B6 mice were intraperitoneally injected with α-GalCer or OCH (an IL4-biased α-GalCer analog) one week prior to the induction of sepsis. To investigate the effects of α-GalCer-mediated iNKT cell activation on sepsis development, immune responses were analyzed by flow cytometry using splenocytes and liver-infiltrating leukocytes. In addition, a STAT6 inhibitor (AS1517499) and an IL10 inhibitor (AS101) were employed to evaluate the involvement of IL4 or IL10 signaling. Furthermore, we performed B cell adoptive transfers to examine the contribution of α-GalCer-induced regulatory B (Breg) cell populations in sepsis protection.Results<jats:italic>In vivo</jats:italic> α-GalCer pretreatment polarized iNKT cells towards IL4- and IL10-producing phenotypes, significantly attenuating LPS/D-GalN-induced septic lethality in WT B6 mice. Furthermore, α-GalCer pretreatment reduced the infiltration of immune cells to the liver and attenuated pro-inflammatory cytokine production. Treatment with a STAT6 inhibitor was unable to modulate disease progression, indicating that IL4 signaling did not significantly affect iNKT cell-mediated protection against sepsis. This finding was confirmed by pretreatment with OCH, which did not alter sepsis outcomes. However, interestingly, prophylactic effects of α-GalCer on sepsis were significantly suppressed by treatment with an IL10 antagonist, suggesting induction of IL10-dependent anti-inflammatory responses. In addition to IL10-producing iNKT cells, IL10-producing B cell populations were significantly increased after α-GalCer pretreatment.ConclusionOverall, our results identify α-GalCer-mediated induction of IL10 by iNKT and B cells as a promising option for controlling the pathogenesis of postoperative sepsis.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1461424
Junhong Chen, Qihang Yuan, Hewen Guan, Yuying Cui, Chang Fu, Tianfu Wei, Kai Liu
BackgroundHepatocellular carcinoma (HCC) is a prevalent and heterogeneous tumor with limited treatment options and unfavorable prognosis. The crucial role of a disintegrin and metalloprotease (ADAM) gene family in the tumor microenvironment of HCC remains unclear.MethodsThis study employed a novel multi-omics integration strategy to investigate the potential roles of ADAM family signals in HCC. A series of single-cell and spatial omics algorithms were utilized to uncover the molecular characteristics of ADAM family genes within HCC. The GSVA package was utilized to compute the scores for ADAM family signals, subsequently stratified into three categories: high, medium, and low ADAM signal levels through unsupervised clustering. Furthermore, we developed and rigorously validated an innovative and robust clinical prognosis assessment model by employing 99 mainstream machine learning algorithms in conjunction with co-expression feature spectra of ADAM family genes. To validate our findings, we conducted PCR and IHC experiments to confirm differential expression patterns within the ADAM family genes.ResultsGene signals from the ADAM family were notably abundant in endothelial cells, liver cells, and monocyte macrophages. Single-cell sequencing and spatial transcriptomics analyses have both revealed the molecular heterogeneity of the ADAM gene family, further emphasizing its significant impact on the development and progression of HCC. In HCC tissues, the expression levels of ADAM9, ADAM10, ADAM15, and ADAM17 were markedly elevated. Elevated ADAM family signal scores were linked to adverse clinical outcomes and disruptions in the immune microenvironment and metabolic reprogramming. An ADAM prognosis signal, developed through the utilization of 99 machine learning algorithms, could accurately forecast the survival duration of HCC, achieving an AUC value of approximately 0.9.ConclusionsThis study represented the inaugural report on the deleterious impact and prognostic significance of ADAM family signals within the tumor microenvironment of HCC.
背景肝细胞癌（HCC）是一种常见的异质性肿瘤，治疗方案有限，预后不良。本研究采用了一种新型的多组学整合策略来研究 ADAM 家族信号在 HCC 中的潜在作用。研究采用了一系列单细胞和空间组学算法来揭示HCC中ADAM家族基因的分子特征。我们利用 GSVA 软件包计算 ADAM 家族信号的得分，然后通过无监督聚类将 ADAM 信号水平分为高、中、低三类。此外，我们还采用了 99 种主流机器学习算法，结合 ADAM 家族基因的共表达特征谱，开发并严格验证了一种创新且稳健的临床预后评估模型。为了验证我们的研究结果，我们进行了 PCR 和 IHC 实验，以确认 ADAM 家族基因的差异表达模式。单细胞测序和空间转录组学分析都揭示了 ADAM 基因家族的分子异质性，进一步强调了其对 HCC 发病和进展的重要影响。在 HCC 组织中，ADAM9、ADAM10、ADAM15 和 ADAM17 的表达水平明显升高。ADAM家族信号得分的升高与不良临床结果、免疫微环境的破坏和代谢重编程有关。这项研究首次报道了 ADAM 家族信号在 HCC 肿瘤微环境中的有害影响和预后意义。
{"title":"Unraveling the role of ADAMs in clinical heterogeneity and the immune microenvironment of hepatocellular carcinoma: insights from single-cell, spatial transcriptomics, and bulk RNA sequencing","authors":"Junhong Chen, Qihang Yuan, Hewen Guan, Yuying Cui, Chang Fu, Tianfu Wei, Kai Liu","doi":"10.3389/fimmu.2024.1461424","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1461424","url":null,"abstract":"BackgroundHepatocellular carcinoma (HCC) is a prevalent and heterogeneous tumor with limited treatment options and unfavorable prognosis. The crucial role of a disintegrin and metalloprotease (ADAM) gene family in the tumor microenvironment of HCC remains unclear.MethodsThis study employed a novel multi-omics integration strategy to investigate the potential roles of ADAM family signals in HCC. A series of single-cell and spatial omics algorithms were utilized to uncover the molecular characteristics of ADAM family genes within HCC. The GSVA package was utilized to compute the scores for ADAM family signals, subsequently stratified into three categories: high, medium, and low ADAM signal levels through unsupervised clustering. Furthermore, we developed and rigorously validated an innovative and robust clinical prognosis assessment model by employing 99 mainstream machine learning algorithms in conjunction with co-expression feature spectra of ADAM family genes. To validate our findings, we conducted PCR and IHC experiments to confirm differential expression patterns within the ADAM family genes.ResultsGene signals from the ADAM family were notably abundant in endothelial cells, liver cells, and monocyte macrophages. Single-cell sequencing and spatial transcriptomics analyses have both revealed the molecular heterogeneity of the ADAM gene family, further emphasizing its significant impact on the development and progression of HCC. In HCC tissues, the expression levels of ADAM9, ADAM10, ADAM15, and ADAM17 were markedly elevated. Elevated ADAM family signal scores were linked to adverse clinical outcomes and disruptions in the immune microenvironment and metabolic reprogramming. An ADAM prognosis signal, developed through the utilization of 99 machine learning algorithms, could accurately forecast the survival duration of HCC, achieving an AUC value of approximately 0.9.ConclusionsThis study represented the inaugural report on the deleterious impact and prognostic significance of ADAM family signals within the tumor microenvironment of HCC.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1397916
Qing Zhang, Xingyu Han, Zhuajin Bi, Mengge Yang, Jing Lin, Zhijun Li, Min Zhang, Bitao Bu
IntroductionNK cells are dysfunctional in myasthenia gravis (MG), but the mechanism is unclear. This study aims to measure associations and underlying mechanisms between the NK cells and the development of MG.MethodsTwenty healthy controls (HCs) and 53 MG patients who did not receive glucocorticoids and immunosuppressants were collected. According to the Myasthenia Gravis Foundation of America (MGFA) classification, MG patients were categorized into MGFA I group (n = 18) and MGFA II-IV group (n = 35). Flow cytometry, cell sorting, ELISA, mRNA-sequencing, RT-qPCR, western blot, and cell culture experiments were performed to evaluate the regulatory mechanism of exhausted NK cells.ResultsPeripheral NK cells in MGFA II-IV patients exhibit exhausted phenotypes than HCs, marked by the dramatic loss of total NK cells, CD56dimCD16− NK cells, elevated PD1 expression, reduced NKG2D expression, impaired cytotoxic activity (perforin, granzyme B, CD107a) and cytokine secretion (IFN-γ). Plasma IL-6 and IL-21 are elevated in MG patients and mainly derived from the aberrant expansion of monocytes and Tfh cells, respectively. IL-6/IL-21 cooperatively induced NK-cell exhausted signature via upregulating SOCS2 and inhibiting the phosphorylation of STAT5. SOCS2 siRNA and IL-2 supplement attenuated the IL-6/IL-21-mediated alteration of NK-cell phenotypes and function.DiscussionInhibition of IL-6/IL-21/SOCS2/STAT5 pathway and recovery of NK-cell ability to inhibit autoimmunity may be a new direction in the treatment of MG.
引言NK细胞在重症肌无力（MG）中功能失调，但其机制尚不清楚。方法收集了20名健康对照组（HCs）和53名未接受糖皮质激素和免疫抑制剂治疗的重症肌无力患者。根据美国肌无力基金会（MGFA）的分类，MG 患者被分为 MGFA I 组（18 人）和 MGFA II-IV 组（35 人）。研究人员通过流式细胞术、细胞分选、ELISA、mRNA测序、RT-qPCR、Western印迹和细胞培养实验来评估衰竭NK细胞的调控机制。结果 MGFA II-IV 患者的外周 NK 细胞比 HCs 表现出衰竭表型，表现为总 NK 细胞、CD56dimCD16- NK 细胞急剧减少，PD1 表达升高，NKG2D 表达降低，细胞毒活性（穿孔素、颗粒酶 B、CD107a）和细胞因子分泌（IFN-γ）受损。MG患者血浆中的IL-6和IL-21升高，主要分别来自单核细胞和Tfh细胞的异常扩增。IL-6/IL-21通过上调SOCS2和抑制STAT5的磷酸化协同诱导NK细胞衰竭特征。讨论抑制IL-6/IL-21/SOCS2/STAT5通路，恢复NK细胞抑制自身免疫的能力可能是治疗MG的一个新方向。
{"title":"Exhausted signature and regulatory network of NK cells in myasthenia gravis","authors":"Qing Zhang, Xingyu Han, Zhuajin Bi, Mengge Yang, Jing Lin, Zhijun Li, Min Zhang, Bitao Bu","doi":"10.3389/fimmu.2024.1397916","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1397916","url":null,"abstract":"IntroductionNK cells are dysfunctional in myasthenia gravis (MG), but the mechanism is unclear. This study aims to measure associations and underlying mechanisms between the NK cells and the development of MG.MethodsTwenty healthy controls (HCs) and 53 MG patients who did not receive glucocorticoids and immunosuppressants were collected. According to the Myasthenia Gravis Foundation of America (MGFA) classification, MG patients were categorized into MGFA I group (n = 18) and MGFA II-IV group (n = 35). Flow cytometry, cell sorting, ELISA, mRNA-sequencing, RT-qPCR, western blot, and cell culture experiments were performed to evaluate the regulatory mechanism of exhausted NK cells.ResultsPeripheral NK cells in MGFA II-IV patients exhibit exhausted phenotypes than HCs, marked by the dramatic loss of total NK cells, CD56<jats:sup>dim</jats:sup>CD16− NK cells, elevated PD1 expression, reduced NKG2D expression, impaired cytotoxic activity (perforin, granzyme B, CD107a) and cytokine secretion (IFN-γ). Plasma IL-6 and IL-21 are elevated in MG patients and mainly derived from the aberrant expansion of monocytes and Tfh cells, respectively. IL-6/IL-21 cooperatively induced NK-cell exhausted signature via upregulating SOCS2 and inhibiting the phosphorylation of STAT5. SOCS2 siRNA and IL-2 supplement attenuated the IL-6/IL-21-mediated alteration of NK-cell phenotypes and function.DiscussionInhibition of IL-6/IL-21/SOCS2/STAT5 pathway and recovery of NK-cell ability to inhibit autoimmunity may be a new direction in the treatment of MG.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1440753
Huili Wu, Lijuan Wang, Chenjie Qiu
ObjectivePatients with rheumatoid arthritis (RA) have an increased risk of developing pulp and periapical disease (PAP), but the causal relationship and shared genetic factors between these conditions have not been explored. This study aimed to investigate the bidirectional causal relationship between RA and PAP and to analyze shared genes and pathogenic pathways.MethodsWe utilized GWAS data from the IEU Open GWAS Project and employed five Mendelian randomization methods (MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) to investigate the bidirectional causal relationship between RA and PAP. Transcriptome data for RA and irreversible pulpitis (IRP) were obtained from the GEO database. Hub genes were identified through differential analysis, CytoHubba, machine learning (ML), and other methods. The immune infiltration of both diseases was analyzed using the ssGSEA method. Finally, we constructed a regulatory network for miRNAs, transcription factors, chemicals, diseases, and RNA-binding proteins based on the identified hub genes.ResultsRA was significantly associated with an increased risk of PAP (OR = 1.1284, 95% CI 1.0674-1.1929, p < 0.001). However, there was insufficient evidence to support the hypothesis that PAP increased the risk of RA. Integrating datasets and differential analysis identified 84 shared genes primarily involved in immune and inflammatory pathways, including the IL-17 signaling pathway, Th17 cell differentiation, and TNF signaling pathway. Using CytoHubba and three ML methods, we identified three hub genes (HLA-DRA, ITGAX, and PTPRC) that are significantly correlated and valuable for diagnosing RA and IRP. We then constructed a comprehensive regulatory network using the miRDB, miRWalk, ChipBase, hTFtarget, CTD, MalaCards, DisGeNET, and ENCORI databases.ConclusionRA may increase the risk of PAP. The three key genes, HLA-DRA, ITGAX, and PTPRC, have significant diagnostic value for both RA and IRP.
目的类风湿性关节炎（RA）患者患牙髓和根尖周病（PAP）的风险增加，但这些疾病之间的因果关系和共有遗传因素尚未得到探讨。本研究旨在研究 RA 和 PAP 之间的双向因果关系，并分析共享基因和致病途径。方法我们利用 IEU 开放 GWAS 项目的 GWAS 数据，并采用五种孟德尔随机方法（MR Egger、加权中位数、逆方差加权、简单模式和加权模式）来研究 RA 和 PAP 之间的双向因果关系。RA 和不可逆牙髓炎（IRP）的转录组数据来自 GEO 数据库。通过差异分析、CytoHubba、机器学习（ML）等方法确定了枢纽基因。使用ssGSEA方法分析了这两种疾病的免疫浸润。最后，我们根据已确定的中心基因构建了一个 miRNA、转录因子、化学物质、疾病和 RNA 结合蛋白的调控网络。RA 与 PAP 风险增加显著相关（OR = 1.1284，95% CI 1.0674-1.1929，pamp &;lt;0.001）。然而，没有足够的证据支持 PAP 会增加 RA 风险的假设。整合数据集和差异分析确定了84个主要参与免疫和炎症通路的共享基因，包括IL-17信号通路、Th17细胞分化和TNF信号通路。利用 CytoHubba 和三种 ML 方法，我们确定了三个枢纽基因（HLA-DRA、ITGAX 和 PTPRC），它们具有显著的相关性，对诊断 RA 和 IRP 很有价值。然后，我们利用 miRDB、miRWalk、ChipBase、hTFtarget、CTD、MalaCards、DisGeNET 和 ENCORI 数据库构建了一个全面的调控网络。HLA-DRA、ITGAX 和 PTPRC 这三个关键基因对 RA 和 IRP 都有重要的诊断价值。
{"title":"Causal relationship, shared genes between rheumatoid arthritis and pulp and periapical disease: evidence from GWAS and transcriptome data","authors":"Huili Wu, Lijuan Wang, Chenjie Qiu","doi":"10.3389/fimmu.2024.1440753","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1440753","url":null,"abstract":"ObjectivePatients with rheumatoid arthritis (RA) have an increased risk of developing pulp and periapical disease (PAP), but the causal relationship and shared genetic factors between these conditions have not been explored. This study aimed to investigate the bidirectional causal relationship between RA and PAP and to analyze shared genes and pathogenic pathways.MethodsWe utilized GWAS data from the IEU Open GWAS Project and employed five Mendelian randomization methods (MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) to investigate the bidirectional causal relationship between RA and PAP. Transcriptome data for RA and irreversible pulpitis (IRP) were obtained from the GEO database. Hub genes were identified through differential analysis, CytoHubba, machine learning (ML), and other methods. The immune infiltration of both diseases was analyzed using the ssGSEA method. Finally, we constructed a regulatory network for miRNAs, transcription factors, chemicals, diseases, and RNA-binding proteins based on the identified hub genes.ResultsRA was significantly associated with an increased risk of PAP (OR = 1.1284, 95% CI 1.0674-1.1929, p &lt; 0.001). However, there was insufficient evidence to support the hypothesis that PAP increased the risk of RA. Integrating datasets and differential analysis identified 84 shared genes primarily involved in immune and inflammatory pathways, including the IL-17 signaling pathway, Th17 cell differentiation, and TNF signaling pathway. Using CytoHubba and three ML methods, we identified three hub genes (HLA-DRA, ITGAX, and PTPRC) that are significantly correlated and valuable for diagnosing RA and IRP. We then constructed a comprehensive regulatory network using the miRDB, miRWalk, ChipBase, hTFtarget, CTD, MalaCards, DisGeNET, and ENCORI databases.ConclusionRA may increase the risk of PAP. The three key genes, HLA-DRA, ITGAX, and PTPRC, have significant diagnostic value for both RA and IRP.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1447608
Efstratios Gavriilidis, Georgios Divolis, Anastasia-Maria Natsi, Nikolaos Kafalis, Dionysios Kogias, Christina Antoniadou, Evgenia Synolaki, Evgenios Pavlos, Marianna A. Koutsi, Stylianos Didaskalou, Evangelos Papadimitriou, Victoria Tsironidou, Ariana Gavriil, Vasileios Papadopoulos, Marios Agelopoulos, Dimitrios Tsilingiris, Maria Koffa, Alexandra Giatromanolaki, Georgios Kouklakis, Konstantinos Ritis, Panagiotis Skendros
IntroductionCrohn’s disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, the disease pathogenesis remains elusive, and the therapeutic options are limited. Here, we investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis, a disease mechanism predisposing to inflammatory and fibrotic complications.MethodsPeripheral neutrophils, enriched neutrophil extracellular traps (eNETs), serum, primary intestinal fibroblasts (PIFs) and intestinal biopsies from CD, ulcerative colitis (UC) patients, and healthy individuals (HI), were studied. Transcriptome analysis of neutrophils, multi-cytokine profiling and cell-based functional assays at mRNA/protein level were performed.ResultsCompared to UC, PIFs from CD patients, independently to the presence of strictures, displayed a distinct pro-fibrotic phenotype characterized by negative Krüppellike Factor-2 (KLF2) and increased cellular communication network factor-2 (CCN2) expression leading to collagen production. In both UC and CD, PIFs-derived IL-8 acted as a culprit chemoattractant for neutrophils in the intestine, where CD neutrophils were accumulated close to fibrotic lesions. Functionally, only CD neutrophils via eNETs induced a CD-like phenotype in HI PIFs, suggesting their fibrotic plasticity. High IFNa in serum and IFΝ-responsive signature in peripheral neutrophils were observed in CD, distinguishing it from UC. Moreover, CD serum stimulated the release of fibrogenic eNETs from neutrophils in an IFNa-dependent manner, suggesting the priming role of IFNa in circulating neutrophils. Inhibition of eNETs or JAK signaling in neutrophils or PIFs prevented the neutrophil-mediated fibrotic effect on PIFs. Furthermore, both serum IFNa levels and mRNA levels of key IFN signaling components in neutrophils were wellcorrelated with CD severity.ConclusionsThis study reveals the important role of the IFNa/neutrophil/fibroblast axis in CD immunofibrosis, suggesting candidate biomarkers and putative therapeutic targets.
导言克罗恩病（CD）的特点是慢性炎症和肠纤维化，会导致终身并发症。然而，该病的发病机制仍然难以捉摸，治疗方案也很有限。方法研究了CD、溃疡性结肠炎（UC）患者和健康人（HI）的外周中性粒细胞、富集的中性粒细胞胞外捕获物（eNETs）、血清、原发性肠成纤维细胞（PIFs）和肠活检组织。结果与 UC 相比，CD 患者的 PIFs 因存在狭窄而表现出明显的促纤维化表型，其特征是 Krüppellike Factor-2 (KLF2) 阴性和细胞通讯网络因子-2 (CCN2) 表达增加，导致胶原蛋白生成。在 UC 和 CD 中，PIFs 衍生的 IL-8 是肠道中性粒细胞的主要趋化吸引因子，其中 CD 中性粒细胞在纤维化病灶附近聚集。从功能上看，只有CD中性粒细胞通过eNETs诱导HI PIFs出现CD样表型，这表明它们具有纤维化可塑性。在 CD 中观察到血清中的高 IFNa 和外周中性粒细胞中的 IFΝ 反应特征，从而将其与 UC 区分开来。此外，CD血清以IFNa依赖性方式刺激中性粒细胞释放纤维化eNETs，这表明IFNa在循环中性粒细胞中起着引物作用。抑制中性粒细胞或 PIF 中的 eNETs 或 JAK 信号转导可阻止中性粒细胞介导的对 PIF 的纤维化作用。结论这项研究揭示了 IFNa/中性粒细胞/成纤维细胞轴在 CD 免疫性纤维化中的重要作用，提出了候选生物标记物和治疗靶点。
{"title":"Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway","authors":"Efstratios Gavriilidis, Georgios Divolis, Anastasia-Maria Natsi, Nikolaos Kafalis, Dionysios Kogias, Christina Antoniadou, Evgenia Synolaki, Evgenios Pavlos, Marianna A. Koutsi, Stylianos Didaskalou, Evangelos Papadimitriou, Victoria Tsironidou, Ariana Gavriil, Vasileios Papadopoulos, Marios Agelopoulos, Dimitrios Tsilingiris, Maria Koffa, Alexandra Giatromanolaki, Georgios Kouklakis, Konstantinos Ritis, Panagiotis Skendros","doi":"10.3389/fimmu.2024.1447608","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1447608","url":null,"abstract":"IntroductionCrohn’s disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, the disease pathogenesis remains elusive, and the therapeutic options are limited. Here, we investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis, a disease mechanism predisposing to inflammatory and fibrotic complications.MethodsPeripheral neutrophils, enriched neutrophil extracellular traps (eNETs), serum, primary intestinal fibroblasts (PIFs) and intestinal biopsies from CD, ulcerative colitis (UC) patients, and healthy individuals (HI), were studied. Transcriptome analysis of neutrophils, multi-cytokine profiling and cell-based functional assays at mRNA/protein level were performed.ResultsCompared to UC, PIFs from CD patients, independently to the presence of strictures, displayed a distinct pro-fibrotic phenotype characterized by negative Krüppellike Factor-2 (KLF2) and increased cellular communication network factor-2 (CCN2) expression leading to collagen production. In both UC and CD, PIFs-derived IL-8 acted as a culprit chemoattractant for neutrophils in the intestine, where CD neutrophils were accumulated close to fibrotic lesions. Functionally, only CD neutrophils via eNETs induced a CD-like phenotype in HI PIFs, suggesting their fibrotic plasticity. High IFNa in serum and IFΝ-responsive signature in peripheral neutrophils were observed in CD, distinguishing it from UC. Moreover, CD serum stimulated the release of fibrogenic eNETs from neutrophils in an IFNa-dependent manner, suggesting the priming role of IFNa in circulating neutrophils. Inhibition of eNETs or JAK signaling in neutrophils or PIFs prevented the neutrophil-mediated fibrotic effect on PIFs. Furthermore, both serum IFNa levels and mRNA levels of key IFN signaling components in neutrophils were wellcorrelated with CD severity.ConclusionsThis study reveals the important role of the IFNa/neutrophil/fibroblast axis in CD immunofibrosis, suggesting candidate biomarkers and putative therapeutic targets.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1431990
Cheng Zhou, Xiaofeng Ye, Zhinuo Liu, Tong Liu, Shanzheng Li, Jinqiu Yang, Jingjing Wei, Peng Yu, Ran Jia, Wenxia Zhao
BackgroundPrevious research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits.MethodsThis study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development.ResultsBased on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps.ConclusionsOur findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.
{"title":"Dissecting the causal links between gut microbiome, immune traits and polyp using genetic evidence","authors":"Cheng Zhou, Xiaofeng Ye, Zhinuo Liu, Tong Liu, Shanzheng Li, Jinqiu Yang, Jingjing Wei, Peng Yu, Ran Jia, Wenxia Zhao","doi":"10.3389/fimmu.2024.1431990","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1431990","url":null,"abstract":"BackgroundPrevious research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits.MethodsThis study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development.ResultsBased on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8<jats:sup>+</jats:sup> T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. <jats:italic>Actinobacteria</jats:italic> remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps.ConclusionsOur findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host’s innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-β promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS‐STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host’s innate immune responses.
{"title":"African swine fever virus MGF360-4L protein attenuates type I interferon response by suppressing the phosphorylation of IRF3","authors":"Zhen Wang, Yuheng He, Ying Huang, Wenzhu Zhai, Chunhao Tao, Yuanyuan Chu, Zhongbao Pang, Hongfei Zhu, Peng Zhao, Hong Jia","doi":"10.3389/fimmu.2024.1382675","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1382675","url":null,"abstract":"African swine fever (ASF) is a highly contagious and lethal disease of swine caused by African swine fever virus (ASFV), and the mortality rate caused by virulent stains can approach 100%. Many ASFV viral proteins suppress the interferon production to evade the host’s innate immune responses. However, whether ASFV MGF360-4L could inhibit type I interferon (IFN-I) signaling pathway and the underlying molecular mechanisms remain unknown. Our study, indicated that ASFV MGF360-4L could negatively regulates the cGAS-STING mediated IFN-I signaling pathway. Overexpressing ASFV MGF360-4L could inhibit the cGAS/STING signaling pathway by inhibiting the interferon-β promoter activity, which was induced by cGAS/STING, TBK1, and IRF3-5D, and further reduced the transcriptional levels of ISG15, ISG54, ISG56, STAT1, STAT2, and TYK2. Confocal microscopy and immunoprecipitation revealed that MGF360-4L co-localized and interacted with IRF3, and WB revealed that ASFV MGF360-4L suppressed the phosphorylation of IRF3. 4L-F2 (75-162 aa) and 4L-F3 (146-387 aa) were the crucial immunosuppressive domains and sites. Altogether, our study reveals ASFV MGF360-4L inhibited cGAS‐STING mediated IFN-I signaling pathways, which provides insights into an evasion strategy of ASFV involving in host’s innate immune responses.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1455691
Liting Yue, Jisong Li, Mingjun Yao, Siyuan Song, Xiaoqin Zhang, Yi Wang
As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation. Additionally, the current availability of islet organ donations fails to meet the demand for organ transplants, making xenotransplantation a crucial method for addressing organ shortages. This review will cover the following three aspects: 1) the immune responses occurring during allogeneic islet transplantation, including three stages: inflammation and IBMIR, allogeneic immune response, and autoimmune recurrence; 2) commonly used immunosuppressants in allogeneic islet transplantation, including calcineurin inhibitors (Cyclosporine A, Tacrolimus), mycophenolate mofetil, glucocorticoids, and Bortezomib; and 3) early and late immune responses in xenogeneic islet transplantation and the immune effects of triple therapy (ECDI-fixed donor spleen cells (ECDI-SP) + anti-CD20 + Sirolimus) on xenotransplantation.
{"title":"Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation","authors":"Liting Yue, Jisong Li, Mingjun Yao, Siyuan Song, Xiaoqin Zhang, Yi Wang","doi":"10.3389/fimmu.2024.1455691","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1455691","url":null,"abstract":"As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation. Additionally, the current availability of islet organ donations fails to meet the demand for organ transplants, making xenotransplantation a crucial method for addressing organ shortages. This review will cover the following three aspects: 1) the immune responses occurring during allogeneic islet transplantation, including three stages: inflammation and IBMIR, allogeneic immune response, and autoimmune recurrence; 2) commonly used immunosuppressants in allogeneic islet transplantation, including calcineurin inhibitors (Cyclosporine A, Tacrolimus), mycophenolate mofetil, glucocorticoids, and Bortezomib; and 3) early and late immune responses in xenogeneic islet transplantation and the immune effects of triple therapy (ECDI-fixed donor spleen cells (ECDI-SP) + anti-CD20 + Sirolimus) on xenotransplantation.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fimmu.2024.1461894
Weimin Xie, Zhengmei Xu
Cervical cancer is one of the most malignant gynaecological tumors characterised with the aggressive behaviour of the tumor cells. In spite of the development of different strategies for the treatment of cervical cancer, the tumor cells have developed resistance to conventional therapeutics. On the other hand, nanoparticles have been recently applied for the treatment of human cancers through delivery of drugs and facilitate tumor suppression. The stimuli-sensitive nanostructures can improve the release of therapeutics at the tumor site. In the present review, the nanostructures for the treatment of cervical cancer are discussed. Nanostructures can deliver both chemotherapy drugs and natural compounds to increase anti-cancer activity and prevent drug resistance in cervical tumor. Moreover, the genetic tools such as siRNA can be delivered by nanoparticles to enhance their accumulation at tumor site. In order to enhance selectivity, the stimuli-responsive nanoparticles such as pH- and redox-responsive nanocarriers have been developed to suppress cervical tumor. Moreover, nanoparticles can induce photo-thermal and photodynamic therapy to accelerate cell death in cervical tumor. In addition, nanobiotechnology demonstrates tremendous potential in the treatment of cervical cancer, especially in the context of tumor immunotherapy. Overall, metal-, carbon-, lipid- and polymer-based nanostructures have been utilized in cervical cancer therapy. Finally, hydrogels have been developed as novel kinds of carriers to encapsulate therapeutics and improve anti-cancer activity.
{"title":"(Nano)biotechnological approaches in the treatment of cervical cancer: integration of engineering and biology","authors":"Weimin Xie, Zhengmei Xu","doi":"10.3389/fimmu.2024.1461894","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1461894","url":null,"abstract":"Cervical cancer is one of the most malignant gynaecological tumors characterised with the aggressive behaviour of the tumor cells. In spite of the development of different strategies for the treatment of cervical cancer, the tumor cells have developed resistance to conventional therapeutics. On the other hand, nanoparticles have been recently applied for the treatment of human cancers through delivery of drugs and facilitate tumor suppression. The stimuli-sensitive nanostructures can improve the release of therapeutics at the tumor site. In the present review, the nanostructures for the treatment of cervical cancer are discussed. Nanostructures can deliver both chemotherapy drugs and natural compounds to increase anti-cancer activity and prevent drug resistance in cervical tumor. Moreover, the genetic tools such as siRNA can be delivered by nanoparticles to enhance their accumulation at tumor site. In order to enhance selectivity, the stimuli-responsive nanoparticles such as pH- and redox-responsive nanocarriers have been developed to suppress cervical tumor. Moreover, nanoparticles can induce photo-thermal and photodynamic therapy to accelerate cell death in cervical tumor. In addition, nanobiotechnology demonstrates tremendous potential in the treatment of cervical cancer, especially in the context of tumor immunotherapy. Overall, metal-, carbon-, lipid- and polymer-based nanostructures have been utilized in cervical cancer therapy. Finally, hydrogels have been developed as novel kinds of carriers to encapsulate therapeutics and improve anti-cancer activity.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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