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Decoding the lncRNA-miRNA-mRNA network in sepsis-induced lung injury: from pathogenesis to extracellular vesicle-based therapy. 解码败血症诱导肺损伤的lncRNA-miRNA-mRNA网络:从发病机制到基于细胞外囊泡的治疗。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1701440
Yating Wei, Weiye Gong, Yuhua Wei, Xiaohong Jiang, Chaoqian Li, Rongzong Ye

Sepsis-induced acute lung injury (S-ALI) represents a life-threatening condition with complex molecular pathophysiology and limited therapeutic options. Emerging evidence highlights the critical role of competing endogenous RNA (ceRNA) networks, particularly long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA axes, in orchestrating cell type-specific responses during S-ALI. This review synthesizes recent advances illustrating how these regulatory circuits modulate alveolar epithelial apoptosis, endothelial permeability, macrophage polarization, and neutrophil infiltration, thereby driving inflammation, barrier dysfunction, and immune dysregulation. Furthermore, we explore the promising therapeutic potential of engineered extracellular vesicles for targeted delivery of ceRNA components-such as miRNA mimics or lncRNA inhibitors-to precisely manipulate these networks. Despite progress, significant challenges remain, including model translatability, functional redundancy, and delivery efficiency. Overcoming these hurdles may unlock novel strategies for treating S-ALI, moving toward personalized and context-specific interventions.

脓毒症引起的急性肺损伤(S-ALI)是一种危及生命的疾病,具有复杂的分子病理生理和有限的治疗选择。新出现的证据强调了竞争性内源性RNA (ceRNA)网络,特别是长链非编码RNA (lncRNA)-microRNA (miRNA)-mRNA轴在S-ALI期间协调细胞类型特异性反应中的关键作用。这篇综述综合了这些调节回路如何调节肺泡上皮细胞凋亡、内皮细胞通透性、巨噬细胞极化和中性粒细胞浸润,从而驱动炎症、屏障功能障碍和免疫失调的最新进展。此外,我们探索了工程细胞外囊泡用于靶向递送ceRNA组分(如miRNA模拟物或lncRNA抑制剂)以精确操纵这些网络的有希望的治疗潜力。尽管取得了进展,但仍然存在重大挑战,包括模型可翻译性、功能冗余和交付效率。克服这些障碍可能会开启治疗S-ALI的新策略,朝着个性化和具体情况干预的方向发展。
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引用次数: 0
Correction: Interactions between the intestinal microbiome and host genes in regulating vibriosis resistance in Cynoglossus semilaevis. 更正:肠道微生物组和宿主基因在调节半舌藻弧菌抗性中的相互作用。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1791642
Weiwei Zheng, Yadong Chen, Tao Yang, Zhihong Liu, Dong Xu, Huizong Han, Yaning Wang, Xiaoqing Xi, Tengteng Wang, Songlin Chen

[This corrects the article DOI: 10.3389/fimmu.2025.1644885.].

[这更正了文章DOI: 10.3389/ fimmune .2025.1644885.]。
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引用次数: 0
B cell phenotypes and antibody signatures associate with interpatient variation in the lung adenocarcinoma tumor microenvironment. B细胞表型和抗体特征与肺腺癌肿瘤微环境的患者间变异有关。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1739637
Kamille M Rasche, David Tieri, Samantha M Morrissey, Hong Li, Fan Zhang, William S Gibson, Easton E Ford, Uddalok Jana, Melissa L Smith, Jun Yan, Corey T Watson

Introduction: Non-small cell lung cancer is the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma (LUAD) as the most common subtype. Although early-stage disease is often treated surgically, advanced LUAD typically requires chemotherapy, radiation, and/or immunotherapy, largely focused on T cell-mediated responses. Therapeutic efficacy, however, is also shaped by tumor-infiltrating (TI) B cells, whose roles in LUAD remain incompletely understood.

Methods: We performed cytometry by time of flight (CyTOF) using 44 markers on matched tumor, adjacent lung, and peripheral blood samples from 48 LUAD patients to define TI immune landscapes. 66 immune cell subsets were identified, and patients were stratified into four groups based on TI cell composition. Adaptive immune receptor repertoire sequencing (AIRR-seq) of IgM and IgG was conducted on matched samples from 29 patients to assess clonal expansion and affinity maturation. Subisotype-resolved AIRR-seq was additionally performed on tumor samples from 18 patients.

Results: CyTOF analysis revealed four patient groups with distinct TI immune profiles. AIRR-seq demonstrated increased clonal expansion and affinity maturation in tumors compared to adjacent lung and blood. Tumor-specific IGHV enrichment patterns were observed but were not associated with patient group assignment. Instead, clonal expansion was greatest in tumors with higher lymphocyte proportions. Subisotype-resolved analysis showed enrichment of IGHG2 and IGHG3 in tumors from patients with low TI B cell abundance, whereas IGHG4 was enriched in patients with high TI B cell infiltration and correlated with four CyTOF-defined immune subsets.

Discussion: These findings reveal substantial inter-individual variation in TI immune landscapes and highlight distinct B cell repertoire and subisotype features within LUAD tumors. Together, these data suggest that B cell composition and antibody subisotype usage may contribute to immune contexture and could inform the development of more tailored immunotherapeutic strategies in LUAD.

非小细胞肺癌是全球癌症相关死亡的主要原因,其中肺腺癌(LUAD)是最常见的亚型。虽然早期疾病通常通过手术治疗,但晚期LUAD通常需要化疗、放疗和/或免疫治疗,主要集中在T细胞介导的反应上。然而,治疗效果也受到肿瘤浸润(TI) B细胞的影响,其在LUAD中的作用尚不完全清楚。方法:采用飞行时间(CyTOF)方法对48例LUAD患者匹配的肿瘤、邻近肺和外周血样本中的44种标志物进行细胞计数,以确定TI免疫景观。鉴定了66个免疫细胞亚群,并根据TI细胞组成将患者分为四组。对来自29例患者的匹配样本进行IgM和IgG的适应性免疫受体库测序(AIRR-seq),以评估克隆扩增和亲和力成熟。此外,对来自18例患者的肿瘤样本进行了亚亚型分辨AIRR-seq。结果:CyTOF分析显示四组患者具有不同的TI免疫谱。与邻近的肺和血液相比,AIRR-seq在肿瘤中显示出更高的克隆扩增和亲和力成熟。观察到肿瘤特异性IGHV富集模式,但与患者组分配无关。相反,克隆扩增在淋巴细胞比例较高的肿瘤中最为明显。亚亚型分辨分析显示,来自低TI B细胞丰度患者的肿瘤中富集IGHG2和IGHG3,而来自高TI B细胞浸润患者的肿瘤中富集IGHG4,并与四种细胞f定义的免疫亚群相关。讨论:这些发现揭示了TI免疫景观的个体间差异,并突出了LUAD肿瘤中不同的B细胞库和亚亚型特征。总之,这些数据表明B细胞组成和抗体亚型的使用可能有助于免疫环境,并可能为LUAD的更有针对性的免疫治疗策略的发展提供信息。
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引用次数: 0
Prognostic impact of advanced lung cancer inflammation index and tumor load index in esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy. 食管鳞状细胞癌新辅助免疫化疗后晚期肺癌炎症指数和肿瘤负荷指数对预后的影响
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1724061
Yizhou Huang, Maohui Chen, Zhenyuan Yang, Yongcong Zhang, Chuanquan Lin, Shuliang Zhang, Taidui Zeng, Jun Yu, Chun Chen, Bin Zheng

Background: Esophageal squamous cell carcinoma (ESCC) carries a high risk of recurrence after neoadjuvant immunochemotherapy and surgery. Both host inflammatory-nutritional status and circulating tumor markers may jointly influence clinical outcomes. We evaluated the prognostic value of the Advanced Lung Cancer Inflammation Index (ALI) and a composite Tumor Load Index (TL) to refine risk stratification in this setting.

Methods: We retrospectively analyzed 460 consecutive ESCC patients who received 2-3 cycles of PD-1 inhibitor plus platinum/taxane-based chemotherapy followed by esophagectomy. ALI was calculated as BMI × albumin/NLR. TL was derived via LASSO Cox regression from pre-treatment SCC-Ag, CEA, and CA19-9. Optimal cutoffs were identified using maximally selected rank statistics (ALI: 31.22; TL: 0.224). Patients were categorized as low-risk (high ALI/low TL), intermediate-risk (high ALI/high TL or low ALI/low TL), and high-risk (low ALI/high TL). Endpoints included overall survival (OS), disease-free survival (DFS), pathologic complete response (pCR), and major pathologic response (MPR).

Results: With a median follow-up of 42 months, 3-year OS rates were 84.7%, 66.0%, and 34.6% for the low-, intermediate-, and high-risk groups, respectively (log-rank P < 0.001). Corresponding 3-year DFS rates were 75.4%, 61.6%, and 29.0%. In multivariable Cox models, intermediate- and high-risk groups had progressively worse OS (adjusted HR = 2.11 and 3.43) and DFS (adjusted HR = 1.64 and 2.62) compared with the low-risk reference (all P < 0.01). High-risk status independently predicted lower odds of achieving MPR (adjusted OR = 0.34, P = 0.002) and pCR (OR = 0.07, P = 0.011). A prognostic nomogram integrating risk group, ASA score, MPR, and ypN status showed strong discrimination (C-index = 0.742) and favorable calibration for 2-, 3-, and 4-year OS, with time-dependent AUCs of 0.759, 0.789, and 0.712.

Conclusions: Pre-treatment ALI and TL jointly provide robust and complementary prognostic information in ESCC patients receiving neoadjuvant immunochemotherapy. Low ALI combined with high TL identifies a biologically aggressive subset with poor pathologic response and inferior survival. Integration of ALI and TL may facilitate risk-adapted perioperative strategies and personalized treatment optimization.

背景:食管鳞状细胞癌(ESCC)在新辅助免疫化疗和手术后具有很高的复发风险。宿主炎症营养状况和循环肿瘤标志物可能共同影响临床结果。我们评估了晚期肺癌炎症指数(ALI)和复合肿瘤负荷指数(TL)的预后价值,以完善这种情况下的风险分层。方法:我们回顾性分析了460例连续接受2-3周期PD-1抑制剂加铂/紫杉烷化疗后食管切除术的ESCC患者。ALI计算为BMI ×白蛋白/NLR。TL通过LASSO Cox回归从预处理后的SCC-Ag、CEA和CA19-9得到。使用最大选择秩统计量确定最佳截止点(ALI: 31.22; TL: 0.224)。患者分为低危(高ALI/低TL)、中危(高ALI/高TL或低ALI/低TL)和高危(低ALI/高TL)。终点包括总生存期(OS)、无病生存期(DFS)、病理完全缓解期(pCR)和主要病理缓解期(MPR)。结果:中位随访42个月,低、中、高风险组3年OS率分别为84.7%、66.0%和34.6% (log-rank P < 0.001)。相应的3年DFS率分别为75.4%、61.6%和29.0%。在多变量Cox模型中,中高危组的OS(调整后的HR = 2.11和3.43)和DFS(调整后的HR = 1.64和2.62)均较低危组恶化(P均< 0.01)。高危状态独立预测实现MPR(校正OR = 0.34, P = 0.002)和pCR (OR = 0.07, P = 0.011)的几率较低。综合风险组、ASA评分、MPR和ypN状态的预后nomogram显示出很强的判别性(C-index = 0.742), 2年、3年和4年OS的校正效果良好,auc随时间变化分别为0.759、0.789和0.712。结论:治疗前ALI和TL联合为接受新辅助免疫化疗的ESCC患者提供了可靠的、互补的预后信息。低ALI合并高TL是一种生物侵袭性亚群,病理反应差,生存率低。整合ALI和TL可以促进风险适应围手术期策略和个性化治疗优化。
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引用次数: 0
Transcriptome and single-cell RNA sequencing analysis with 101 machine learning combinations and experimental verification reveals the mechanism of action of mannose metabolism in bladder cancer. 101机器学习组合转录组和单细胞RNA测序分析以及实验验证揭示了甘露糖代谢在膀胱癌中的作用机制。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1710823
Anhong Li, Kaile Zhao, Tianjiao Wang, Guangyue Shi

Background: Bladder cancer (BLCA) is a prevalent genitourinary malignancy characterized by high recurrence and mortality rates. While mannose metabolism has demonstrated anti-tumor potential across various cancers, its role in BLCA remains underexplored. This study examines the influence of mannose metabolism on BLCA prognosis.

Methods: BLCA-related datasets and genes associated with mannose metabolism (MMRGs) were obtained from public databases. Candidate genes were identified by overlapping differentially expressed genes with MMRGs. Prognostic genes were pinpointed using ten machine learning algorithms and regression analysis to develop a risk model, which was subsequently validated. A nomogram was constructed by integrating the risk score with clinical features, and its predictive accuracy was assessed. We performed functional enrichment, drug sensitivity, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, immunohistochemistry, and immune infiltration analyses. Key cellular components were identified, and further analyses, including pathway enrichment, pseudo-temporal analysis, and cell communication, were performed.

Results: CALR, SLMAP, PFKFB4, and TMTC1 were identified as prognostic genes in BLCA. Notably, the expression of SLMAP and TMTC1 was significantly downregulated in BLCA, whereas PFKFB4 and CALR were upregulated. These findings were consistently validated by RT-qPCR, Western blotting, and immunohistochemical analyses (p < 0.05). The risk model stratified patients into a high-risk group (HRG) and a low-risk group (LRG), with HRG patients exhibiting significantly poorer survival outcomes. The risk score was identified as an independent prognostic factor, and the nomogram demonstrated high diagnostic accuracy. Notable differences between HRG and LRG patients were observed in the "Ribosome" pathway. Additionally, 86 chemotherapeutic drugs exhibited significant differential responses between HRG and LRG, with 23 immune cell types showing differential abundances, including activated dendritic cells (p < 0.05). Single-cell analysis revealed macrophages as key cells in BLCA, which were classified into five subtypes, with CALR, SLMAP, and PFKFB4 influencing their expression.

Conclusion: Four mannose metabolism-related prognostic genes were identified in BLCA, and macrophages were confirmed as critical cells. These findings provide valuable insights for improving prognostic assessment in BLCA.

背景:膀胱癌(BLCA)是一种常见的泌尿生殖系统恶性肿瘤,具有高复发率和高死亡率。虽然甘露糖代谢在多种癌症中显示出抗肿瘤潜力,但其在BLCA中的作用仍未得到充分研究。本研究探讨甘露糖代谢对BLCA预后的影响。方法:从公共数据库获取blca相关数据集和甘露糖代谢相关基因(MMRGs)。候选基因是通过与MMRGs重叠差异表达基因来鉴定的。使用十种机器学习算法和回归分析来确定预后基因,以开发风险模型,并随后进行验证。将风险评分与临床特征相结合构建nomogram,并对其预测准确性进行评估。我们进行了功能富集、药物敏感性、逆转录-定量聚合酶链反应(RT-qPCR)、免疫印迹、免疫组织化学和免疫浸润分析。鉴定了关键的细胞成分,并进行了进一步的分析,包括途径富集、伪时间分析和细胞通讯。结果:CALR、SLMAP、PFKFB4和TMTC1被确定为BLCA的预后基因。值得注意的是,SLMAP和TMTC1的表达在BLCA中显著下调,而PFKFB4和CALR的表达上调。RT-qPCR、Western blotting和免疫组织化学分析一致证实了这些发现(p < 0.05)。风险模型将患者分为高风险组(HRG)和低风险组(LRG), HRG患者的生存结果明显较差。风险评分被确定为一个独立的预后因素,nomogram诊断准确性高。HRG和LRG患者在“核糖体”途径上观察到显著差异。此外,86种化疗药物在HRG和LRG之间表现出显著差异反应,23种免疫细胞类型表现出不同的丰度,包括活化的树突状细胞(p < 0.05)。单细胞分析显示巨噬细胞是BLCA的关键细胞,可分为5个亚型,CALR、SLMAP和PFKFB4影响其表达。结论:在BLCA中发现了4个甘露糖代谢相关的预后基因,并证实巨噬细胞是关键细胞。这些发现为改善BLCA的预后评估提供了有价值的见解。
{"title":"Transcriptome and single-cell RNA sequencing analysis with 101 machine learning combinations and experimental verification reveals the mechanism of action of mannose metabolism in bladder cancer.","authors":"Anhong Li, Kaile Zhao, Tianjiao Wang, Guangyue Shi","doi":"10.3389/fimmu.2026.1710823","DOIUrl":"10.3389/fimmu.2026.1710823","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BLCA) is a prevalent genitourinary malignancy characterized by high recurrence and mortality rates. While mannose metabolism has demonstrated anti-tumor potential across various cancers, its role in BLCA remains underexplored. This study examines the influence of mannose metabolism on BLCA prognosis.</p><p><strong>Methods: </strong>BLCA-related datasets and genes associated with mannose metabolism (MMRGs) were obtained from public databases. Candidate genes were identified by overlapping differentially expressed genes with MMRGs. Prognostic genes were pinpointed using ten machine learning algorithms and regression analysis to develop a risk model, which was subsequently validated. A nomogram was constructed by integrating the risk score with clinical features, and its predictive accuracy was assessed. We performed functional enrichment, drug sensitivity, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, immunohistochemistry, and immune infiltration analyses. Key cellular components were identified, and further analyses, including pathway enrichment, pseudo-temporal analysis, and cell communication, were performed.</p><p><strong>Results: </strong>CALR, SLMAP, PFKFB4, and TMTC1 were identified as prognostic genes in BLCA. Notably, the expression of SLMAP and TMTC1 was significantly downregulated in BLCA, whereas PFKFB4 and CALR were upregulated. These findings were consistently validated by RT-qPCR, Western blotting, and immunohistochemical analyses (p < 0.05). The risk model stratified patients into a high-risk group (HRG) and a low-risk group (LRG), with HRG patients exhibiting significantly poorer survival outcomes. The risk score was identified as an independent prognostic factor, and the nomogram demonstrated high diagnostic accuracy. Notable differences between HRG and LRG patients were observed in the \"Ribosome\" pathway. Additionally, 86 chemotherapeutic drugs exhibited significant differential responses between HRG and LRG, with 23 immune cell types showing differential abundances, including activated dendritic cells (p < 0.05). Single-cell analysis revealed macrophages as key cells in BLCA, which were classified into five subtypes, with CALR, SLMAP, and PFKFB4 influencing their expression.</p><p><strong>Conclusion: </strong>Four mannose metabolism-related prognostic genes were identified in BLCA, and macrophages were confirmed as critical cells. These findings provide valuable insights for improving prognostic assessment in BLCA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1710823"},"PeriodicalIF":5.9,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A skin isolate of Micrococcus luteus negates the Staphylococcus aureus-induced release of type 2 cytokines from keratinocytes. 皮肤分离的黄体微球菌可抑制金黄色葡萄球菌诱导的角质形成细胞释放2型细胞因子。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1711723
Abigail E Elias, Joanne L Pennock, Andrew J McBain, Emma-Jayne Keevill, Catherine A O'Neill

Staphylococcus aureus second immunoglobulin-binding protein (Sbi) is a unique type 2-promoting virulence factor that induces IL-33 and thymic stromal lymphopoietin (TSLP) release. This mechanism is essential for the development of S. aureus-induced eczema in the widely used NC/Tnd mouse model of human atopic dermatitis (AD). Microbiome shifts in AD suggest that microbiota could modulate the disease. We therefore sought to identify skin bacteria that attenuate S. aureus-induced IL-33/TSLP release from keratinocytes. Micrococcus luteus was unique among skin isolates in its ability to negate cytokine induction. The bioactive factor responsible was identified using fractionation, LC-MS and recombinant proteins, as the serine protease "PA domain protein" (PADP). Immunoblotting and ELISA confirmed Sbi and IL-33 degradation by PADP. This was not observed with the M. luteus type strain which contains a frame shift mutation within the PADP active site. These data provide new insights into the role of skin microbiota in AD and highlights their potential as topical therapeutics.

金黄色葡萄球菌第二免疫球蛋白结合蛋白(Sbi)是一种独特的2型促毒因子,可诱导IL-33和胸腺基质淋巴生成素(TSLP)的释放。在广泛应用的NC/Tnd人特应性皮炎(AD)小鼠模型中,这一机制对金黄色葡萄球菌诱导的湿疹的发展至关重要。阿尔茨海默病中微生物群的变化表明微生物群可以调节疾病。因此,我们试图鉴定皮肤细菌,以减少金黄色葡萄球菌诱导的角质形成细胞释放IL-33/TSLP。在皮肤分离物中,黄体微球菌是独特的,因为它具有否定细胞因子诱导的能力。通过分离、LC-MS和重组蛋白鉴定其生物活性因子为丝氨酸蛋白酶“PA结构域蛋白”(PADP)。免疫印迹和酶联免疫吸附法证实了PADP对Sbi和IL-33的降解作用。这在黄体分枝杆菌型菌株中没有观察到,该菌株在PADP活性位点内含有帧移位突变。这些数据为皮肤微生物群在AD中的作用提供了新的见解,并强调了它们作为局部治疗药物的潜力。
{"title":"A skin isolate of <i>Micrococcus luteus</i> negates the <i>Staphylococcus aureus-</i>induced release of type 2 cytokines from keratinocytes.","authors":"Abigail E Elias, Joanne L Pennock, Andrew J McBain, Emma-Jayne Keevill, Catherine A O'Neill","doi":"10.3389/fimmu.2026.1711723","DOIUrl":"10.3389/fimmu.2026.1711723","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> second immunoglobulin-binding protein (Sbi) is a unique type 2-promoting virulence factor that induces IL-33 and thymic stromal lymphopoietin (TSLP) release. This mechanism is essential for the development of <i>S. aureus</i>-induced eczema in the widely used NC/Tnd mouse model of human atopic dermatitis (AD). Microbiome shifts in AD suggest that microbiota could modulate the disease. We therefore sought to identify skin bacteria that attenuate <i>S. aureus-</i>induced IL-33/TSLP release from keratinocytes. <i>Micrococcus luteus</i> was unique among skin isolates in its ability to negate cytokine induction. The bioactive factor responsible was identified using fractionation, LC-MS and recombinant proteins, as the serine protease \"PA domain protein\" (PADP). Immunoblotting and ELISA confirmed Sbi and IL-33 degradation by PADP. This was not observed with the <i>M. luteus</i> type strain which contains a frame shift mutation within the PADP active site. These data provide new insights into the role of skin microbiota in AD and highlights their potential as topical therapeutics.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1711723"},"PeriodicalIF":5.9,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
B-cell epitope mapping and characterization of antibody responses to recombinant PvRipr in malaria-exposed individuals. 疟疾暴露个体中重组PvRipr抗体反应的b细胞表位定位和表征。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1710869
Isabela Ferreira Soares, Cinthia Magalhães Rodolphi, Ana Luiza Carneiro Alencar, Ada da Silva Matos, Rodrigo Nunes Rodrigues-da-Silva, Barbara de Oliveira Baptista, Rodrigo Medeiros Martorano, Hugo Amorim Dos Santos de Souza, Evelyn Kety Pratt Riccio, Jenifer Peixoto de Barros, Paulo Renato Rivas Totino, Cláudio Tadeu Daniel-Ribeiro, Lilian Rose Pratt-Riccio, Josué da Costa Lima-Junior

Introduction: Malaria caused by P. vivax continues to be a serious public health problem, especially in countries like Brazil where P. vivax accounts for more than 80% of diagnosed cases. Since this plasmodial species is characterized as one of the most difficult to eliminate, the development of a specific vaccine for P. vivax may be an essential tool for effective control of the disease. The protein Ripr has been described in P. falciparum as an essential part of the erythrocyte invasion complex. Given the limited number of P. vivax vaccine antigens currently under investigation, this study aimed to characterize, the naturally acquired humoral immune response to Ripr protein of P. vivax.

Methods: ELISA assays were performed using plasma samples from individuals naturally exposed to malaria in the Brazilian Amazon in order to determine levels of IgM, IgG and IgG subclasses against PvRipr. In addition, linear B-cell epitopes within the protein were identified.

Results and discussion: Our results demonstrated that PvRipr is naturally immunogenic, as more than 60% of the individuals presented IgM or IgG antibodies against recombinant PvRipr. The profile of IgG subclasses was also investigated and higher frequencies of seropositive individuals for IgG1 and IgG2 were observed. After in silico prediction, a total of four linear B cell epitopes were identified in PvRipr, from these sequences, B-PvRipr(879-888) and B-PvRipr(923-958) had higher frequencies of seropositive individuals and reactivity indexes in comparison to the other tested epitopes. Moreover, levels of IgG antibodies specific for these two epitopes were strongly correlated with the levels of IgG antibodies against recombinant PvRipr and especially with IgG3 antibodies, a cytophilic subclass widely cited in the protective immune response against malaria.

导言:间日疟原虫引起的疟疾仍然是一个严重的公共卫生问题,特别是在巴西这样的国家,间日疟原虫占确诊病例的80%以上。由于间日疟原虫是最难消灭的疟原虫之一,开发针对间日疟原虫的特异性疫苗可能是有效控制该疾病的重要工具。在恶性疟原虫中,Ripr蛋白已被描述为红细胞侵袭复合物的重要组成部分。鉴于目前正在研究的间日疟原虫疫苗抗原数量有限,本研究旨在表征间日疟原虫对Ripr蛋白的自然获得性体液免疫反应。方法:使用巴西亚马逊地区自然暴露于疟疾的个体的血浆样本进行ELISA检测,以确定抗PvRipr的IgM、IgG和IgG亚类的水平。此外,还鉴定了该蛋白内的线性b细胞表位。结果和讨论:我们的结果表明,PvRipr具有天然的免疫原性,因为超过60%的个体存在针对重组PvRipr的IgM或IgG抗体。IgG亚类的分布也进行了调查,观察到IgG1和IgG2血清阳性个体的频率较高。经过计算机预测,在PvRipr中共鉴定出4个线性B细胞表位,从这些序列中,B-PvRipr(879-888)和B-PvRipr(923-958)的血清阳性个体频率和反应性指数高于其他检测的表位。此外,针对这两个表位的IgG抗体水平与针对重组PvRipr的IgG抗体水平密切相关,特别是与IgG3抗体(一种在疟疾保护性免疫反应中广泛引用的亲细胞亚类)的水平密切相关。
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引用次数: 0
Altered genome induced immune response of iPSCs. 改变基因组诱导iPSCs的免疫应答。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1751499
Jordi Requena Osete, Belén Álvarez Palomo, Michael J Edel
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引用次数: 0
The metastasis landscape of Clonorchis sinensis-associated hepatocellular carcinoma: an integrated multi-omics and clinical study. 华支睾吸虫相关性肝癌的转移格局:一项综合多组学和临床研究
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1723156
Lingling Zhou, Lin Sun, Xuhang Huang, Junxian Chen, Taijun Huang, Yulong Xu, Xiaorong Luo, Caibiao Wei, Fengfei Liu, Xiaolan Pan, Madanni Dong, Jingyu Su, Weilong Yang, Min Fang

Background: Hepatocellular carcinoma (HCC) patients with Clonorchis sinensis (Cs) infection tend to exhibit a poorer prognosis compared to those without infection. Nevertheless, the molecular mechanisms underlying Cs-associated HCC, particularly those linked to metastatic progression, remain poorly understood. This study therefore seeks to elucidate the role of C. sinensis infection in promoting metastasis.

Methods: Through a clinical retrospective analysis, we compared overall survival and metastasis incidence between HCC patients with and without Cs infection. To explore the underlying mechanisms, we conducted integrated multi-omics analyses-including RNA-seq, miRNA-seq, ATAC-seq, WGBS-seq, oxWGBS-seq, and ChIP-seq-to profile 369 metastasis-related genes in Cs + and Cs - HCC tumors. The expression of three key metastasis-related genes was further validated by RT-qPCR, and Transwell and wound-healing assays were performed in vitro to confirm the pro-metastatic effect of Cs infection on HCC cells.

Results: In HCC patients, Cs infection was associated with poorer overall survival and an increased metastasis rate. We identified 20 metastasis-related genes, with SPP1, MMP2, and VCAM1 as central hubs, together with 41 interacting miRNAs and 71 accessible promoter regions. Histone modifications-particularly H3K9ac, H3K27ac and H3K4me3-were correlated with chromatin accessibility in the promoters of these genes. Molecular experiments further demonstrated that Cs infection enhances the metastatic potential of HCC.

Conclusions: Our study reveals that Cs infection promotes HCC metastasis through gene and epigenetic alterations, providing mechanistic insights and identifying potential targets for early intervention.

背景:肝细胞癌(HCC)患者合并华支睾吸虫(Cs)感染的预后比未感染的患者差。然而,cs相关性HCC的分子机制,特别是与转移进展相关的分子机制,仍然知之甚少。因此,本研究旨在阐明中华梭菌感染在促进转移中的作用。方法:通过临床回顾性分析,比较HCC合并和未合并Cs感染患者的总生存率和转移发生率。为了探索潜在的机制,我们进行了综合多组学分析,包括RNA-seq、miRNA-seq、ATAC-seq、WGBS-seq、oxWGBS-seq和chip -seq,以分析Cs +和Cs - HCC肿瘤中369个转移相关基因。通过RT-qPCR进一步验证3个关键转移相关基因的表达,并通过体外Transwell和创面愈合实验证实Cs感染对HCC细胞的促转移作用。结果:在HCC患者中,Cs感染与较差的总生存期和增加的转移率相关。我们确定了20个转移相关基因,其中SPP1、MMP2和VCAM1为中心枢纽,以及41个相互作用的mirna和71个可访问的启动子区域。组蛋白修饰——尤其是H3K9ac、H3K27ac和h3k4me3——与这些基因启动子的染色质可及性相关。分子实验进一步证明,Cs感染增强了HCC的转移潜能。结论:我们的研究揭示了Cs感染通过基因和表观遗传改变促进HCC转移,提供了机制见解并确定了早期干预的潜在靶点。
{"title":"The metastasis landscape of <i>Clonorchis sinensis</i>-associated hepatocellular carcinoma: an integrated multi-omics and clinical study.","authors":"Lingling Zhou, Lin Sun, Xuhang Huang, Junxian Chen, Taijun Huang, Yulong Xu, Xiaorong Luo, Caibiao Wei, Fengfei Liu, Xiaolan Pan, Madanni Dong, Jingyu Su, Weilong Yang, Min Fang","doi":"10.3389/fimmu.2026.1723156","DOIUrl":"10.3389/fimmu.2026.1723156","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) patients with <i>Clonorchis sinensis</i> (<i>Cs</i>) infection tend to exhibit a poorer prognosis compared to those without infection. Nevertheless, the molecular mechanisms underlying <i>Cs</i>-associated HCC, particularly those linked to metastatic progression, remain poorly understood. This study therefore seeks to elucidate the role of <i>C. sinensis</i> infection in promoting metastasis.</p><p><strong>Methods: </strong>Through a clinical retrospective analysis, we compared overall survival and metastasis incidence between HCC patients with and without <i>Cs</i> infection. To explore the underlying mechanisms, we conducted integrated multi-omics analyses-including RNA-seq, miRNA-seq, ATAC-seq, WGBS-seq, oxWGBS-seq, and ChIP-seq-to profile 369 metastasis-related genes in <i>Cs</i> <sup>+</sup> and <i>Cs</i> <sup>-</sup> HCC tumors. The expression of three key metastasis-related genes was further validated by RT-qPCR, and Transwell and wound-healing assays were performed <i>in vitro</i> to confirm the pro-metastatic effect of <i>Cs</i> infection on HCC cells.</p><p><strong>Results: </strong>In HCC patients, <i>Cs</i> infection was associated with poorer overall survival and an increased metastasis rate. We identified 20 metastasis-related genes, with <i>SPP1</i>, <i>MMP2</i>, and <i>VCAM1</i> as central hubs, together with 41 interacting miRNAs and 71 accessible promoter regions. Histone modifications-particularly H3K9ac, H3K27ac and H3K4me3-were correlated with chromatin accessibility in the promoters of these genes. Molecular experiments further demonstrated that <i>Cs</i> infection enhances the metastatic potential of HCC.</p><p><strong>Conclusions: </strong>Our study reveals that <i>Cs</i> infection promotes HCC metastasis through gene and epigenetic alterations, providing mechanistic insights and identifying potential targets for early intervention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1723156"},"PeriodicalIF":5.9,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The stem of Schisandra chinensis and Schisandrin B alleviated DNCB-induced atopic dermatitis in mice by inhibiting the NF-κB pathway. 五味子茎和五味子素B通过抑制NF-κB通路减轻dncb诱导的小鼠特应性皮炎。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1725312
Cai Ye, Yijie Liu, Yue Li, Zan Li, Liyuan Sui, Jiwen Cui, Zihao Jiang, Jinlian Li, Jianjun Song, Jiguang Liu

Background: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disorder. While the stem of Schisandra chinensis has been extensively studied for its pharmacological properties, including anti-inflammatory, antioxidant, and hepatoprotective effects, its therapeutic potential in AD remains to be elucidated. This study therefore aimed to investigate the effects of Schisandra chinensis stem extract (SCSE) against AD and to explore its underlying mechanism of action.

Methods: Chemical profiling of SCSE via UPLC-Q-Exactive-Orbitrap-MS revealed 45 constituents, with lignans comprising 80%. The primary active component was identified through activity-guided assays employing hyaluronidase inhibition and HPLC. The therapeutic efficacy of SCSE and its constituent Schisandrin B (Sch B) was assessed in an AD mouse model. Furthermore, network pharmacology predicted the involved signaling pathways, and these predictions were subsequently validated experimentally.

Results: Sch B was identified as the core active component. Both SCSE and Sch B significantly improved skin barrier function in AD mice, as evidenced by reduced transepidermal water loss (TEWL) and upregulation of key barrier proteins (Filaggrin, Loricrin, and Claudin-1). They also alleviated pruritus by suppressing Transient Receptor Potential Vanilloid 1 (TRPV1) and mitigated the allergic-inflammatory response, as shown by reduced Immunoglobulin E (IgE) levels and inhibited release of mast cell (MC) mediators (IL-4, IL-6, TNF-α). These effects were potentially mediated through modulation of the NF-κB pathway.

Conclusion: By simultaneously mitigating skin barrier dysfunction, immune inflammation, and pruritus, SCSE and Sch B hold promise as therapeutic candidates capable of disrupting the self-perpetuating cycle of AD. These findings position SCSE and Sch B as a novel therapeutic strategy for this disease.

背景:特应性皮炎(AD)是一种慢性、瘙痒性、炎症性皮肤疾病。虽然五味子茎的药理特性已被广泛研究,包括抗炎、抗氧化和肝保护作用,但其治疗AD的潜力仍有待阐明。本研究旨在探讨五味子提取物(Schisandra chinensis stem extract, SCSE)抗AD的作用机制。方法:通过UPLC-Q-Exactive-Orbitrap-MS对SCSE进行化学分析,发现45种成分,其中木脂素占80%。主要有效成分通过透明质酸酶抑制和高效液相色谱法的活性指导分析确定。在AD小鼠模型中评估SCSE及其成分五味子素B (Schisandrin B, Sch B)的治疗效果。此外,网络药理学预测了相关的信号通路,这些预测随后得到了实验验证。结果:经鉴定为核心活性成分。SCSE和Sch B均能显著改善AD小鼠的皮肤屏障功能,这可以通过减少经皮失水(TEWL)和上调关键屏障蛋白(聚丝蛋白、Loricrin和Claudin-1)来证明。通过降低免疫球蛋白E (IgE)水平和抑制肥大细胞(MC)介质(IL-4、IL-6、TNF-α)的释放,它们还可以通过抑制瞬时受体电位香草样蛋白1 (TRPV1)和减轻过敏炎症反应来缓解瘙痒。这些作用可能是通过调节NF-κB途径介导的。结论:通过同时减轻皮肤屏障功能障碍、免疫炎症和瘙痒,SCSE和Sch B有望成为能够破坏AD自我延续周期的候选治疗药物。这些发现表明SCSE和Sch B是一种新的治疗策略。
{"title":"The stem of <i>Schisandra chinensis</i> and Schisandrin B alleviated DNCB-induced atopic dermatitis in mice by inhibiting the NF-κB pathway.","authors":"Cai Ye, Yijie Liu, Yue Li, Zan Li, Liyuan Sui, Jiwen Cui, Zihao Jiang, Jinlian Li, Jianjun Song, Jiguang Liu","doi":"10.3389/fimmu.2026.1725312","DOIUrl":"10.3389/fimmu.2026.1725312","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disorder. While the stem of Schisandra chinensis has been extensively studied for its pharmacological properties, including anti-inflammatory, antioxidant, and hepatoprotective effects, its therapeutic potential in AD remains to be elucidated. This study therefore aimed to investigate the effects of <i>Schisandra chinensis</i> stem extract (SCSE) against AD and to explore its underlying mechanism of action.</p><p><strong>Methods: </strong>Chemical profiling of SCSE via UPLC-Q-Exactive-Orbitrap-MS revealed 45 constituents, with lignans comprising 80%. The primary active component was identified through activity-guided assays employing hyaluronidase inhibition and HPLC. The therapeutic efficacy of SCSE and its constituent Schisandrin B (Sch B) was assessed in an AD mouse model. Furthermore, network pharmacology predicted the involved signaling pathways, and these predictions were subsequently validated experimentally.</p><p><strong>Results: </strong>Sch B was identified as the core active component. Both SCSE and Sch B significantly improved skin barrier function in AD mice, as evidenced by reduced transepidermal water loss (TEWL) and upregulation of key barrier proteins (Filaggrin, Loricrin, and Claudin-1). They also alleviated pruritus by suppressing Transient Receptor Potential Vanilloid 1 (TRPV1) and mitigated the allergic-inflammatory response, as shown by reduced Immunoglobulin E (IgE) levels and inhibited release of mast cell (MC) mediators (IL-4, IL-6, TNF-α). These effects were potentially mediated through modulation of the NF-κB pathway.</p><p><strong>Conclusion: </strong>By simultaneously mitigating skin barrier dysfunction, immune inflammation, and pruritus, SCSE and Sch B hold promise as therapeutic candidates capable of disrupting the self-perpetuating cycle of AD. These findings position SCSE and Sch B as a novel therapeutic strategy for this disease.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1725312"},"PeriodicalIF":5.9,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12890654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Frontiers in Immunology
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