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Increased infiltration of CD4+ T cell in the complement deficient lymphedema model. 补体缺乏型淋巴水肿模型中CD4+T细胞浸润增加。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-11-08 DOI: 10.1186/s12865-023-00580-1
Toshihiko Nishioka, Kei-Ichi Katayama, Shinji Kumegawa, Kyoichi Isono, Takashi Baba, Hiroshi Tsujimoto, Gen Yamada, Norimitsu Inoue, Shinichi Asamura

Background: Lymphedema is an intractable disease that can be caused by injury to lymphatic vessels, such as by surgical treatments for cancer. It can lead to impaired joint mobility in the extremities and reduced quality of life. Chronic inflammation due to infiltration of various immune cells in an area of lymphedema is thought to lead to local fibrosis, but the molecular pathogenesis of lymphedema remains unclear. Development of effective therapies requires elucidation of the immunological mechanisms involved in the progression of lymphedema. The complement system is part of the innate immune system which has a central role in the elimination of invading microbes and acts as a scavenger of altered host cells, such as apoptotic and necrotic cells and cellular debris. Complement-targeted therapies have recently been clinically applied to various diseases caused by complement overactivation. In this context, we aimed to determine whether complement activation is involved in the development of lymphedema.

Results: Our mouse tail lymphedema models showed increased expression of C3, and that the classical or lectin pathway was locally activated. Complement activation was suggested to be involved in the progression of lymphedema. In comparison of the C3 knockout (KO) mouse lymphedema model and wild-type mice, there was no difference in the degree of edema at three weeks postoperatively, but the C3 KO mice had a significant increase of TUNEL+ necrotic cells and CD4+ T cells. Infiltration of macrophages and granulocytes was not significantly elevated in C3 KO or C5 KO mice compared with in wild-type mice. Impaired opsonization and decreased migration of macrophages and granulocytes due to C3 deficiency should therefore induce the accumulation of dead cells and may lead to increased infiltration of CD4+ T cells.

Conclusions: Vigilance for exacerbation of lymphedema is necessary when surgical treatments have the potential to injure lymphatic vessels in patients undergoing complement-targeted therapies or with complement deficiency. Future studies should aim to elucidate the molecular mechanism of CD4+ T cell infiltration by accumulated dead cells.

背景:淋巴水肿是一种棘手的疾病,可由淋巴管损伤引起,如癌症的外科治疗。它会导致四肢关节活动能力受损,生活质量下降。淋巴水肿区域各种免疫细胞浸润引起的慢性炎症被认为会导致局部纤维化,但淋巴水肿的分子发病机制尚不清楚。开发有效的治疗方法需要阐明淋巴水肿进展的免疫机制。补体系统是先天免疫系统的一部分,在消除入侵微生物方面发挥核心作用,并作为改变的宿主细胞(如凋亡和坏死细胞以及细胞碎片)的清除剂。补体靶向治疗最近已在临床上应用于由补体过度激活引起的各种疾病。在这种情况下,我们旨在确定补体激活是否参与淋巴水肿的发展。结果:我们的小鼠尾部淋巴水肿模型显示C3的表达增加,并且经典或凝集素途径被局部激活。补体激活被认为与淋巴水肿的进展有关。与C3敲除(KO)小鼠淋巴水肿模型和野生型小鼠相比,术后三周的水肿程度没有差异,但C3敲除小鼠的TUNEL+坏死细胞和CD4+T细胞显著增加。与野生型小鼠相比,C3 KO或C5 KO小鼠中巨噬细胞和粒细胞的浸润没有显著升高。因此,C3缺乏导致的巨噬细胞和粒细胞的调理作用受损和迁移减少应诱导死细胞的积累,并可能导致CD4+T细胞的浸润增加。结论:当接受补体靶向治疗或补体缺乏患者的手术治疗可能损伤淋巴管时,有必要警惕淋巴水肿的恶化。未来的研究应旨在阐明CD4+T细胞通过积累的死细胞浸润的分子机制。
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引用次数: 0
Vitamin D and biomarkers of inflammation and oxidative stress among pregnant women: a systematic review of observational studies. 维生素D与孕妇炎症和氧化应激的生物标志物:观察性研究的系统综述。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-27 DOI: 10.1186/s12865-023-00577-w
Soudabe Motamed, Razieh Anari, Somayeh Motamed, Reza Amani

Objective: This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.

Methods: Three databases (PubMed/MEDLINE, Scopus, and Web of Science (WoS)) and reference list of included documents were searched for related observational studies published until 2nd October 2023. To determine the quality of the selected observational studies, the Newcastle-Ottawa Scale (NOS) was used.

Results: After a primary search of three databases, 19492records were appeared. When duplicates and irrelevant documents were removed, 14 articles were found to have eligible criteria. The design of the identified studies was cross-sectional, case-control and cohort. Evidence showed an adverse association between 25(OH)D and the biomarkers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor- alfa (TNF-α) during pregnancy. On the contrary, some studies represented that 25(OH)D positively correlated with hs-CRP in the cord blood. One study suggested a direct association between serum concentrations of 25(OH)D and Interleukin-8 (IL-8), macrophage inflammatory protein (MIP), and TNF-α levels in mothers with gestational diabetes mellitus (GDM). A case-control study showed that lower serum concentration of 25(OH)D positively correlated with total antioxidant capacity (TAC) levels in participants.

Conclusions: Evidence confirmed the supposition of the direct relationship between vitamin D levels and biomarkers with anti-inflammatory and anti-oxidative properties. However, the Existence of inconsistent evidence confirms the need for further studies in mothers with GDM and hypertensive disorders.

Prospero registration code: CRD42020202600.

目的:本系统综述旨在绘制评估维生素D与妊娠期氧化还原和炎症状态之间关系的证据。方法:检索三个数据库(PubMed/MEDLINE、Scopus和Web of Science(WoS))和收录文献的参考文献列表,查找截至2023年10月2日发表的相关观察性研究。为了确定所选观察性研究的质量,使用了纽卡斯尔-渥太华量表(NOS)。结果:在对三个数据库进行初步检索后,共出现19492条记录。当删除重复和不相关的文件时,发现14篇文章符合条件。已确定的研究采用横断面、病例对照和队列设计。有证据表明,25(OH)D与妊娠期炎症的生物标志物,如高敏C反应蛋白(hs-CRP)、白细胞介素-1β(IL-1β)、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)之间存在不良关联。相反,一些研究表明,25(OH)D与脐血中的hs-CRP呈正相关。一项研究表明,妊娠期糖尿病(GDM)母亲的血清25(OH)D浓度、白细胞介素-8(IL-8)、巨噬细胞炎症蛋白(MIP)和TNF-α水平之间存在直接关联。一项病例对照研究表明,参与者血清中较低的25(OH)D浓度与总抗氧化能力(TAC)水平呈正相关。结论:有证据证实了维生素D水平与具有抗炎和抗氧化特性的生物标志物之间存在直接关系的假设。然而,不一致证据的存在证实了对患有GDM和高血压疾病的母亲进行进一步研究的必要性。Prospero注册代码:CRD42020202600。
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引用次数: 0
The upregulation of peripheral CD3-CD56+CD16+ natural killer cells correlates with Th1/Th2 imbalance in asthma patients during acute upper respiratory viral infections. 急性上呼吸道病毒感染期间哮喘患者外周CD3-CD56+CD16+自然杀伤细胞的上调与Th1/Th2失衡相关。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-21 DOI: 10.1186/s12865-023-00575-y
Meixuan Liu, Yunxuan Zhang, Yunqian Hu, Zhongliang Guo, Lin Dong

Purpose: The aim of this study is to clarify the changes of peripheral CD3-CD56+CD16+ NK cells and their correlation with Th1/Th2 immunity profiles in asthma during the phase of acute upper respiratory viral infections (AURVIs).

Methods: Peripheral venous blood and induced sputum samples were collected from 56 mild asthma patients, 49 asthma patients with AURVIs and 50 healthy subjects. Peripheral CD3-CD56+CD16+ NK cells were monitored by flow cytometry during the course of acute viral infections. Meanwhile, the induced sputum Th2 cytokines IL-4 and IL-5, and Th1 cytokine IFN-γ were also detected by ELISA assay.

Results: The asthmatics had lower levels of peripheral CD3-CD56+CD16+ NK cells populations as well as higher induced sputum cytokines (IL-4, IL-5 and IFN-γ) compared to healthy controls at baseline. Upon upper respiratory viral infections, peripheral CD3-CD56+CD16+ NK cells numbers in asthma patients sharply elevated on day 3 and slowly decreased by day 14, in accordance with induced sputum IFN-γ changes. IL-4 and IL-5 levels spiked much later (day 8) and lasted until day 14. Compared with asthma alone group, the IFN-γ/IL-4 and IFN-γ/IL-5 ratios of the asthma patients with AURVIs on day 1 were higher and peaked on day 3. The changes of peripheral CD3-CD56+CD16+ NK cells proportions positively correlated with the IFN-γ/IL-4 and IFN-γ/IL-5 ratios on day 1 to day 3 in asthma subsequent to upper respiratory viral infections.

Conclusions: Our findings showed an imbalanced Th1/Th2 immunity in airways of asthma with acute upper respiratory viral infections. Upregulated peripheral CD3-CD56+CD16+ NK cells play a crucial role in biased Th1 immunity of airways in asthma during the acute phase of viral infections. The anti-viral Th1 immunity by targeting NK cells may be a possible therapeutic option for virus-induced asthma exacerbation.

目的:本研究旨在阐明急性上呼吸道病毒感染(AURVIs)期间哮喘患者外周CD3-CD56+CD16+NK细胞的变化及其与Th1/Th2免疫谱的相关性。在急性病毒感染过程中通过流式细胞术监测外周CD3-CD56+CD16+NK细胞。同时,ELISA法检测诱导痰中Th2细胞因子IL-4和IL-5,以及Th1细胞因子IFN-γ。结果:与基线健康对照组相比,哮喘患者外周CD3-CD56+CD16+NK细胞群水平较低,诱导的痰液细胞因子(IL-4、IL-5和IFN-γ)水平较高。在上呼吸道病毒感染后,哮喘患者的外周CD3-CD56+CD16+NK细胞数量在第3天急剧增加,在第14天缓慢减少,这与诱导的痰IFN-γ变化一致。IL-4和IL-5水平在很久之后(第8天)飙升并持续到第14天。与单纯哮喘组相比,AURVIs哮喘患者在第1天的IFN-γ/IL-4和IFN-γ-IL-5比值较高,并在第3天达到峰值。外周CD3-CD56+CD16+NK细胞比例的变化与上呼吸道病毒感染后哮喘第1天至第3天的IFN-γ/IL-4和IFN-γ/IL-5比例呈正相关。结论:我们的研究结果显示,急性上呼吸道病毒感染的哮喘气道中Th1/Th2免疫失衡。在病毒感染的急性期,上调的外周CD3-CD56+CD16+NK细胞在哮喘气道的偏向性Th1免疫中起着至关重要的作用。通过靶向NK细胞的抗病毒Th1免疫可能是病毒诱导的哮喘恶化的一种可能的治疗选择。
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引用次数: 0
Humoral immune response and changes in peritoneal cell populations in rats immunized against two Leptospira serovars; serovar patoc and serovar pyrogenes. 两种钩端螺旋体血清型免疫大鼠的体液免疫反应和腹膜细胞群的变化;patoc血清型和热原血清型。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-17 DOI: 10.1186/s12865-023-00574-z
Dakshika Gangani, Wathsala Dissanayake, Rajiva de Silva, Kaushalya Anuradha, Lilani Karunanayake, Narmada Fernando, Senaka Rajapakse, Sunil Premawansa, Shiroma Handunnetti

Background: Leptospirosis is a zoonotic disease caused by Leptospira species. Variations in lipopolysaccharide (LPS) structure in Leptospira are known to be associated with the serovar diversity and antigenicity. Development of immunodiagnostics for early detection of leptospirosis based on immune responses against different pathogenic antigens as well as development of vaccines are important. Hence, this study has assessed the immune response generated against leptospiral LPS and whole antigen preparations of pathogenic and saprophytic Leptospira and specific changes in peritoneal cells was also studied to elucidate the cellular responses associated with immune response of Wistar rats.

Methods: During the study, immune response induced by two types of Leptospira antigen preparations of two selected serovars was compared. Changes in the specific peritoneal cell subpopulations following immunizations of rats were analyzed using flow cytometry.

Results: Of the two antigen preparations tested, the LPS extract induced a higher IgM immune response as opposed to the sonicated antigen preparation. Of the two serovars tested, L. interrogans serovar Pyrogenes had induced a higher IgM response compared to that by L. biflexa serovar Patoc. Considering the IgG titers, equivalent responses were observed with all four antigen preparations. Significant increases in lymphocytes were observed following immunization with LPS of both serovars. Interestingly, the B2 cell percentages increased significantly during the immunization period. Further, significant correlations were observed with both IgM and IgG responses and percentage of B2 cells in the peritoneal cavity (PC).

Conclusion: LPS extract of L. interrogans serovar Pyrogenes induced higher IgM response while the IgG response was equivalent among the four antigen preparations tested. Significant increase of B2 cell percentage in the peritoneal cavity during the immunization reflects the accumulation of B2 cells in the PC which may play considerable role in generating humoral response against Leptospira antigens.

背景:钩端螺旋体病是由钩端螺旋菌引起的一种人畜共患疾病。已知钩端螺旋体脂多糖(LPS)结构的变化与血清型多样性和抗原性有关。基于对不同致病抗原的免疫反应开发用于早期检测钩端螺旋体病的免疫诊断以及开发疫苗是重要的。因此,本研究评估了针对致病性和腐生性钩端螺旋体的钩端螺旋LPS和全抗原制剂产生的免疫反应,并研究了腹膜细胞的特异性变化,以阐明与Wistar大鼠免疫反应相关的细胞反应。方法:在研究过程中,比较两种血清型钩端螺旋体抗原制剂诱导的免疫反应。用流式细胞术分析大鼠免疫后腹膜特定细胞亚群的变化。结果:在测试的两种抗原制剂中,与超声处理的抗原制剂相比,LPS提取物诱导了更高的IgM免疫反应。在测试的两种血清变异株中,与双弯乳杆菌血清变异株Patoc相比,询问乳杆菌Pyrogenes血清变异株诱导了更高的IgM反应。考虑到IgG滴度,所有四种抗原制剂均观察到等效反应。在用LPS免疫两种血清型后,观察到淋巴细胞的显著增加。有趣的是,B2细胞百分比在免疫期间显著增加。此外,IgM和IgG反应以及腹腔内B2细胞的百分比也存在显著相关性。免疫过程中腹腔中B2细胞百分比的显著增加反映了B2细胞在PC中的积累,这可能在产生针对钩端螺旋体抗原的体液反应中发挥相当大的作用。
{"title":"Humoral immune response and changes in peritoneal cell populations in rats immunized against two Leptospira serovars; serovar patoc and serovar pyrogenes.","authors":"Dakshika Gangani, Wathsala Dissanayake, Rajiva de Silva, Kaushalya Anuradha, Lilani Karunanayake, Narmada Fernando, Senaka Rajapakse, Sunil Premawansa, Shiroma Handunnetti","doi":"10.1186/s12865-023-00574-z","DOIUrl":"10.1186/s12865-023-00574-z","url":null,"abstract":"<p><strong>Background: </strong>Leptospirosis is a zoonotic disease caused by Leptospira species. Variations in lipopolysaccharide (LPS) structure in Leptospira are known to be associated with the serovar diversity and antigenicity. Development of immunodiagnostics for early detection of leptospirosis based on immune responses against different pathogenic antigens as well as development of vaccines are important. Hence, this study has assessed the immune response generated against leptospiral LPS and whole antigen preparations of pathogenic and saprophytic Leptospira and specific changes in peritoneal cells was also studied to elucidate the cellular responses associated with immune response of Wistar rats.</p><p><strong>Methods: </strong>During the study, immune response induced by two types of Leptospira antigen preparations of two selected serovars was compared. Changes in the specific peritoneal cell subpopulations following immunizations of rats were analyzed using flow cytometry.</p><p><strong>Results: </strong>Of the two antigen preparations tested, the LPS extract induced a higher IgM immune response as opposed to the sonicated antigen preparation. Of the two serovars tested, L. interrogans serovar Pyrogenes had induced a higher IgM response compared to that by L. biflexa serovar Patoc. Considering the IgG titers, equivalent responses were observed with all four antigen preparations. Significant increases in lymphocytes were observed following immunization with LPS of both serovars. Interestingly, the B2 cell percentages increased significantly during the immunization period. Further, significant correlations were observed with both IgM and IgG responses and percentage of B2 cells in the peritoneal cavity (PC).</p><p><strong>Conclusion: </strong>LPS extract of L. interrogans serovar Pyrogenes induced higher IgM response while the IgG response was equivalent among the four antigen preparations tested. Significant increase of B2 cell percentage in the peritoneal cavity during the immunization reflects the accumulation of B2 cells in the PC which may play considerable role in generating humoral response against Leptospira antigens.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"24 1","pages":"39"},"PeriodicalIF":3.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Methionine enkephalin(MENK) upregulated memory T cells in anti-influenza response. 甲硫氨酸脑啡肽(MENK)在抗流感反应中上调记忆T细胞。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-12 DOI: 10.1186/s12865-023-00573-0
Jing Tian, Wenrui Fu, Zifeng Xie, Xiaonan Wang, Miao Miao, Fengping Shan, Xiaodong Yu

Novel prophylactic drugs and vaccination strategies for protection against influenza virus should induce specific effector T-cell immune responses in pulmonary airways and peripheral lymphoid organs. Designing approaches that promote T-cell-mediated responses and memory T-cell differentiation would strengthen host resistance to respiratory infectious diseases. The results of this study showed that pulmonary delivery of MENK via intranasal administration reduced viral titres, upregulated opioid receptor MOR and DOR, increased the proportions of T-cell subsets including CD8+ T cells, CD8+ TEM cells, NP/PA-effector CD8+ TEM cells in bronchoalveolar lavage fluid and lungs, and CD4+/CD8+ TCM cells in lymph nodes to protect mice against influenza viral challenge. Furthermore, we demonstrated that, on the 10th day of infection, the proportions of CD4+ TM and CD8+ TM cells were significantly increased, which meant that a stable TCM and TEM lineage was established in the early stage of influenza infection. Collectively, our data suggested that MENK administered intranasally, similar to the route of natural infection by influenza A virus, could exert antiviral activity through upregulating T-cell-mediated adaptive immune responses against influenza virus.

预防流感病毒的新型预防药物和疫苗接种策略应在肺气道和外周淋巴器官中诱导特异性效应T细胞免疫反应。设计促进T细胞介导的反应和记忆T细胞分化的方法将增强宿主对呼吸道传染病的抵抗力。本研究的结果表明,通过鼻内给药的MENK肺部给药降低了病毒滴度,上调了阿片受体MOR和DOR,增加了支气管肺泡灌洗液和肺部T细胞亚群的比例,包括CD8+T细胞、CD8+TEM细胞、NP/PA效应CD8+TEM细胞,以及淋巴结中的CD4+/CD8+TCM细胞,以保护小鼠免受流感病毒攻击。此外,我们证明,在感染的第10天,CD4+TM和CD8+TM细胞的比例显著增加,这意味着在流感感染的早期阶段建立了稳定的TCM和TEM谱系。总之,我们的数据表明,类似于甲型流感病毒的自然感染途径,鼻内给药MENK可以通过上调T细胞介导的针对流感病毒的适应性免疫反应来发挥抗病毒活性。
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引用次数: 0
Transcriptomic analysis identifies CYP27A1 as a diagnostic marker for the prognosis and immunity in lung adenocarcinoma. 转录组学分析确定CYP27A1是肺腺癌预后和免疫的诊断标志物。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-10 DOI: 10.1186/s12865-023-00572-1
Yi Yin, Muqun He, Yunjian Huang, Xianhe Xie

Background: The association between lipid metabolism disorder and carcinogenesis is well-established, but there is limited research on the connection between lipid metabolism-related genes (LRGs) and lung adenocarcinoma (LUAD). The objective of our research was to identify LRGs as the potential biomarkers for prognosis and assess their impact on immune cell infiltration in LUAD.

Methods: We identified novel prognostic LRGs for LUAD patients via the bioinformatics analysis. CYP27A1 expression level was systematically evaluated via various databases, such as TCGA, UALCAN, and TIMER. Subsequently, LinkedOmics was utilized to perform the CYP27A1 co-expression network and GSEA. ssGSEA was conducted to assess the association between infiltration of immune cells and CYP27A1 expression. CYP27A1's expression level was validated by qRT-PCR analysis.

Results: CYP27A1 expression was decreased in LUAD. Reduced CYP27A1 expression was linked to unfavorable prognosis in LUAD. Univariate and multivariate analyses indicated that CYP27A1 was an independent prognostic biomarker for LUAD patients. GSEA results revealed a positive correlation between CYP27A1 expression and immune-related pathways. Furthermore, CYP27A1 expression was positively correlated with the infiltration levels of most immune cells.

Conclusion: CYP27A1 is a potential biomarker for LUAD patients, and our findings provided a novel perspective to develop the prognostic marker for LUAD patients.

背景:脂质代谢紊乱与致癌作用之间的联系已经得到证实,但对脂质代谢相关基因(LRGs)与肺腺癌(LUAD)之间的联系的研究有限。我们的研究目的是确定LRG作为潜在的预后生物标志物,并评估其对LUAD免疫细胞浸润的影响。方法:通过生物信息学分析,我们为LUAD患者确定了新的预后LRG。CYP27A1的表达水平通过各种数据库进行系统评估,如TCGA、UALCAN和TIMER。随后,利用LinkedOmics进行CYP27A1共表达网络和GSEA。进行ssGSEA以评估免疫细胞浸润与CYP27A1表达之间的相关性。通过qRT-PCR分析验证CYP27A1的表达水平。结果:CYP27A1在LUAD中的表达降低。CYP27A1表达降低与LUAD的不良预后有关。单变量和多变量分析表明CYP27A1是LUAD患者的独立预后生物标志物。GSEA结果显示CYP27A1的表达与免疫相关途径呈正相关。此外,CYP27A1的表达与大多数免疫细胞的浸润水平呈正相关。结论:CYP27A1是LUAD患者潜在的生物标志物,我们的研究结果为开发LUAD患者的预后标志物提供了新的视角。
{"title":"Transcriptomic analysis identifies CYP27A1 as a diagnostic marker for the prognosis and immunity in lung adenocarcinoma.","authors":"Yi Yin, Muqun He, Yunjian Huang, Xianhe Xie","doi":"10.1186/s12865-023-00572-1","DOIUrl":"10.1186/s12865-023-00572-1","url":null,"abstract":"<p><strong>Background: </strong>The association between lipid metabolism disorder and carcinogenesis is well-established, but there is limited research on the connection between lipid metabolism-related genes (LRGs) and lung adenocarcinoma (LUAD). The objective of our research was to identify LRGs as the potential biomarkers for prognosis and assess their impact on immune cell infiltration in LUAD.</p><p><strong>Methods: </strong>We identified novel prognostic LRGs for LUAD patients via the bioinformatics analysis. CYP27A1 expression level was systematically evaluated via various databases, such as TCGA, UALCAN, and TIMER. Subsequently, LinkedOmics was utilized to perform the CYP27A1 co-expression network and GSEA. ssGSEA was conducted to assess the association between infiltration of immune cells and CYP27A1 expression. CYP27A1's expression level was validated by qRT-PCR analysis.</p><p><strong>Results: </strong>CYP27A1 expression was decreased in LUAD. Reduced CYP27A1 expression was linked to unfavorable prognosis in LUAD. Univariate and multivariate analyses indicated that CYP27A1 was an independent prognostic biomarker for LUAD patients. GSEA results revealed a positive correlation between CYP27A1 expression and immune-related pathways. Furthermore, CYP27A1 expression was positively correlated with the infiltration levels of most immune cells.</p><p><strong>Conclusion: </strong>CYP27A1 is a potential biomarker for LUAD patients, and our findings provided a novel perspective to develop the prognostic marker for LUAD patients.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"24 1","pages":"37"},"PeriodicalIF":3.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10565965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1
Bcl-3 regulates T cell function through energy metabolism. Bcl-3通过能量代谢调节T细胞功能。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-04 DOI: 10.1186/s12865-023-00570-3
Hui Liu, Lin Zeng, Mengmeng Pan, Liwenhui Huang, Hanying Li, Mengxia Liu, Xinqing Niu, Chenguang Zhang, Hui Wang

Background: Bcl-3 is a member of the IκB protein family and an essential modulator of NF-κB activity. It is well established that Bcl-3 is critical for the normal development, survival and differentiation of adaptive immune cells, especially T cells. However, the regulation of immune cell function by Bcl-3 through metabolic pathways has rarely been studied.

Results: In this study, we explored the role of Bcl-3 in the metabolism and function of T cells via the mTOR pathway. We verified that the proliferation of Bcl-3-deficient Jurkat T cells was inhibited, but their activation was promoted, and Bcl-3 depletion regulated cellular energy metabolism by reducing intracellular ATP and ROS production levels and mitochondrial membrane potential. Bcl-3 also regulates cellular energy metabolism in naive CD4+ T cells. In addition, the knockout of Bcl-3 altered the expression of mTOR, Akt, and Raptor, which are metabolism-related genes, in Jurkat cells.

Conclusions: This finding indicates that Bcl-3 may mediate the energy metabolism of T cells through the mTOR pathway, thereby affecting their function. Overall, we provide novel insights into the regulatory role of Bcl-3 in T-cell energy metabolism for the prevention and treatment of immune diseases.

背景:Bcl-3是IκB蛋白家族的成员,也是NF-κB活性的重要调节剂。Bcl-3对适应性免疫细胞,特别是T细胞的正常发育、存活和分化至关重要。然而,Bcl-3通过代谢途径调节免疫细胞功能的研究很少。结果:在本研究中,我们通过mTOR途径探讨了Bcl-3在T细胞代谢和功能中的作用。我们证实Bcl-3缺陷的Jurkat T细胞的增殖受到抑制,但它们的激活被促进,Bcl-3缺失通过降低细胞内ATP和ROS的产生水平以及线粒体膜电位来调节细胞能量代谢。Bcl-3还调节幼稚CD4+T细胞的细胞能量代谢。此外,Bcl-3的敲除改变了Jurkat细胞中代谢相关基因mTOR、Akt和Raptor的表达。结论:Bcl-3可能通过mTOR途径介导T细胞的能量代谢,从而影响其功能。总之,我们对Bcl-3在T细胞能量代谢中的调节作用提供了新的见解,用于预防和治疗免疫疾病。
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引用次数: 0
The digestive system and autoimmunity. 消化系统和自身免疫。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-10-04 DOI: 10.1186/s12865-023-00561-4
Lina Sun, Baojun Zhang

Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection "The digestive system and autoimmunity".

消化系统自身免疫性疾病对全球健康构成越来越大的挑战。与自身免疫性消化系统疾病相关的危险因素是复杂的,包括遗传变异、免疫功能障碍和各种环境因素。为了更好地了解消化系统自身免疫性疾病背后的机制,包括引起胃肠道表现和发病机制的因素,BMC免疫学推出了一个新的集合“消化系统和自身免疫”。
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引用次数: 0
Function and autophagy of monocyte-derived dendritic cells is affected by hepatitis B virus infection. 单核细胞来源的树突状细胞的功能和自噬受到乙型肝炎病毒感染的影响。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-09-26 DOI: 10.1186/s12865-023-00571-2
Hua Xu, Juan Kang, Shan Zhong, Min Chen, Peng Hu, Hong Ren, Zhi Zhou, Yu Lei

Background: The role of dendritic cells and the autophagy state of dendritic cells in the immune response of hepatitis B virus (HBV) infection was still controversial. In this study, we carefully examined the phenotype, function and autophagy pathway of dendritic cells in HBV infection.

Methods: Monocyte-derived dendritic cells from healthy blood donors and patients with chronic HBV infection were stimulated by lipopolysaccharide, supernatant of HepG2.2.15 cells or supernatant of HepG2 cells respectively. Phenotype of dendritic cells was examined by flow cytometry and cytokines secretion was detected by enzyme-linked immunosorbent assay. Autophagy related proteins were detected by western blot and immunofluorescence analysis.

Results: Our results showed that the expression of both major histocompatibility complex II molecules and co-stimulated molecules including cluster of differentiation antigen 80, cluster of differentiation antigen 86 in the monocyte-derived dendritic cells from patients with chronic HBV infection was significantly higher than that from healthy donors when cultured with supernatant of HepG2.2.15 cells. The amount of cytokines, including tumour necrosis factor-α, interleukin-10 and interleukin-12, secreted by monocyte-derived dendritic cells from patients with chronic HBV infection was also significantly higher than that from healthy donors when stimulate by HBV. Interestingly, the expression level of autophagy-related proteins including autophagy-related protein5 and associated protein 1 light chain in dendritic cells from patients with chronic HBV infection was significantly increased when compared with that from healthy donors when re-exposed to HBV.

Conclusions: Our results indicated that dendritic cells from patients with chronic HBV infection could intensively present antigen and express co-stimulatory molecules. The increased activation of dendritic cells might be related to the enhanced autophagy of dendritic cells in HBV infection.

背景:树突状细胞和树突状细胞的自噬状态在乙型肝炎病毒(HBV)感染的免疫反应中的作用仍然存在争议。在本研究中,我们仔细检查了HBV感染中树突状细胞的表型、功能和自噬途径。方法:分别用脂多糖、HepG2.2.15细胞上清液和HepG2细胞上清液刺激健康献血者和慢性HBV感染者的单核细胞来源的树突状细胞。流式细胞仪检测树突状细胞表型,酶联免疫吸附法检测细胞因子分泌。通过蛋白质印迹和免疫荧光分析检测自噬相关蛋白。结果:主要组织相容性复合体II分子和共刺激分子(包括分化抗原簇80,当与HepG2.2.15细胞的上清液培养时,来自慢性HBV感染患者的单核细胞衍生的树突状细胞中的分化抗原簇86显著高于来自健康供体的分化抗原。当HBV刺激时,慢性HBV感染患者的单核细胞衍生的树突状细胞分泌的细胞因子,包括肿瘤坏死因子-α、白细胞介素-10和白细胞介质-12的量也显著高于健康供体。有趣的是,与健康供体相比,慢性HBV感染患者树突状细胞中自噬相关蛋白(包括自噬相关蛋白质5和相关蛋白质1轻链)的表达水平显著升高呈递抗原并表达共刺激分子。树突状细胞活化的增加可能与HBV感染中树突状细胞自噬的增强有关。
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引用次数: 0
The development of a highly sensitive and quantitative SARS-CoV-2 rapid antigen test applying newly developed monoclonal antibodies to an automated chemiluminescent flow-through membrane immunoassay device. 将新开发的单克隆抗体应用于自动化学发光流通膜免疫测定装置的高度灵敏和定量的严重急性呼吸系统综合征冠状病毒2型快速抗原检测的开发。
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2023-09-26 DOI: 10.1186/s12865-023-00567-y
Kengo Nishimura, Hiroaki Kitazawa, Takashi Kawahata, Kosuke Yuhara, Takahiro Masuya, Toshihiro Kuroita, Kentarou Waki, Seiichi Koike, Masaharu Isobe, Nobuyuki Kurosawa

Background: Rapid and accurate diagnosis of individuals with SARS-CoV-2 infection is an effective way to prevent and control the spread of COVID-19. Although the detection of SARS-CoV-2 viral RNA by RT-qPCR is the gold standard for COVID-19 testing, the use of antigen-detecting rapid diagnostic tests (Ag-RDTs) is emerging as a complementary surveillance tool as Omicron case numbers skyrocket worldwide. However, the results from Ag-RDTs are less accurate in individuals with low viral loads.

Results: To develop a highly sensitive and accurate Ag-RDT, 90 monoclonal antibodies were raised from guinea pigs immunized with SARS CoV-2 nucleocapsid protein (CoV-2-NP). By applying a capture antibody recognizing the structural epitope of the N-terminal domain of CoV-2-NP and a detection antibody recognizing the C-terminal tail of CoV-2-NP to an automated chemiluminescence flow-through membrane immunoassay device, we developed a novel Ag-RDT, CoV-2-POCube. The CoV-2-POCube exclusively recognizes CoV-2-NP variants but not the nucleocapsid proteins of other human coronaviruses. The CoV-2-POCube achieved a limit of detection sensitivity of 0.20 ~ 0.66 pg/mL of CoV-2-NPs, demonstrating more than 100 times greater sensitivity than commercially available SARS-CoV-2 Ag-RDTs.

Conclusions: CoV-2-POCube has high analytical sensitivity and can detect SARS-CoV-2 variants in 15 min without observing the high-dose hook effect, thus meeting the need for early SARS-CoV-2 diagnosis with lower viral load. CoV-2-POCube is a promising alternative to currently available diagnostic devices for faster clinical decision making in individuals with suspected COVID-19 in resource-limited settings.

背景:快速准确地诊断SARS-CoV-2感染者是预防和控制新冠肺炎传播的有效途径。尽管RT-qPCR检测SARS-CoV-2病毒RNA是新冠肺炎检测的金标准,但随着全球奥密克戎病例数飙升,抗原检测快速诊断检测(Ag-RDT)的使用正在成为一种补充监测工具。然而,Ag-RDT的结果在病毒载量低的个体中不太准确。结果:从SARS冠状病毒2型核衣壳蛋白(CoV-2-NP)免疫的豚鼠身上制备了90株单克隆抗体,建立了一种高灵敏、准确的Ag-RDT。通过将识别CoV-2-NP N端结构域结构表位的捕获抗体和识别CoV-2-NP C端尾部的检测抗体应用于自动化学发光流通膜免疫测定装置,我们开发了一种新型的Ag-RDT,CoV-2-POCube。CoV-2-POCube只识别CoV-2-NP变体,但不识别其他人类冠状病毒的核衣壳蛋白。CoV-2-POCube实现了0.20的检测灵敏度极限 ~ 0.66 pg/mL的CoV-2-NP,显示出比市售的严重急性呼吸系统综合征冠状病毒2型Ag-RDT高100多倍的灵敏度。CoV-2-POCube是目前可用诊断设备的一种很有前途的替代品,可以在资源有限的环境中为疑似新冠肺炎患者更快地做出临床决策。
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引用次数: 0
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BMC Immunology
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