Discovery immunology最新文献

Identification of a transcription factor network regulating anti-TNF mediated IL10 expression in human CD4+ T cells 识别调控人类 CD4+ T 细胞中由抗肿瘤坏死因子介导的 IL10 表达的转录因子网络

Discovery immunology Pub Date : 2024-07-27 DOI: 10.1093/discim/kyae013

G. A. Povoleri, M. Ridley, Rebecca J Marrow, Sylvine Lalnunhlimi, Sarah E. Ryan, Audrey Kelly, Paul Lavender, L. Taams

{"title":"Identification of a transcription factor network regulating anti-TNF mediated IL10 expression in human CD4+ T cells","authors":"G. A. Povoleri, M. Ridley, Rebecca J Marrow, Sylvine Lalnunhlimi, Sarah E. Ryan, Audrey Kelly, Paul Lavender, L. Taams","doi":"10.1093/discim/kyae013","DOIUrl":"https://doi.org/10.1093/discim/kyae013","url":null,"abstract":"\u0000 CD4+ T cells are key players in immune-mediated inflammatory diseases (IMIDs) through production of inflammatory mediators including TNF. Anti-TNF therapy has revolutionised the treatment of several IMIDs and we previously demonstrated that in vitro treatment of human CD4+ T cells with anti-TNF promotes anti-inflammatory IL-10 expression in multiple subpopulations of CD4+ T cells. Here we investigated the transcriptional mechanisms underlying the IL-10 induction by TNF-blockade in CD4+ T cells, isolated from PBMCs of healthy volunteers, stimulated in vitro for 3 days with anti-CD3/CD28 mAb in the absence or presence of anti-TNF. After culture, CD45RA+ cells were depleted before performing gene expression profiling and chromatin accessibility analysis. Gene expression analysis of CD45RA-CD4+ T cells showed a distinct anti-TNF specific gene signature of 183 genes (q-value <0.05). Pathway enrichment analysis of differentially expressed genes revealed multiple pathways related to cytokine signalling and regulation of cytokine production; in particular, IL10 was the most upregulated gene by anti-TNF, while the proinflammatory cytokines and chemokines IFNG, IL9, IL22 and CXCL10 were significantly downregulated (q-value <0.05). Transcription factor motif analysis at the differentially open chromatin regions, after anti-TNF treatment, revealed 58 transcription factor motifs enriched at the IL10 locus. We identified seven transcription factor candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF treatment. Correlation analysis between the expression of these transcription factors and IL10 suggests a role for MAF, PRDM1 and/or EOMES in regulating IL10 expression in CD4+ T cells upon anti-TNF treatment.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141798170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback. 更正：淡水三刺鱼免疫系统的月相生物节律

Discovery immunology Pub Date : 2024-07-15 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae012

引用次数: 0

Assessing immune phenotypes using simple proxy measures: promise and limitations. 使用简单的替代措施评估免疫表型：前景与局限。

Discovery immunology Pub Date : 2024-06-28 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae010

Alexander E Downie, Ramya S Barre, Annie Robinson, Jennie Yang, Ying-Han Chen, Jian-Da Lin, Oyebola Oyesola, Frank Yeung, Ken Cadwell, P'ng Loke, Andrea L Graham

{"title":"Assessing immune phenotypes using simple proxy measures: promise and limitations.","authors":"Alexander E Downie, Ramya S Barre, Annie Robinson, Jennie Yang, Ying-Han Chen, Jian-Da Lin, Oyebola Oyesola, Frank Yeung, Ken Cadwell, P'ng Loke, Andrea L Graham","doi":"10.1093/discim/kyae010","DOIUrl":"10.1093/discim/kyae010","url":null,"abstract":"The study of immune phenotypes in wild animals is beset by numerous methodological challenges, with assessment of detailed aspects of phenotype difficult to impossible. This constrains the ability of disease ecologists and ecoimmunologists to describe immune variation and evaluate hypotheses explaining said variation. The development of simple approaches that allow characterization of immune variation across many populations and species would be a significant advance. Here we explore whether serum protein concentrations and coarse-grained white blood cell profiles, immune quantities that can easily be assayed in many species, can predict, and therefore serve as proxies for, lymphocyte composition properties. We do this in rewilded laboratory mice, which combine the benefits of immune phenotyping of lab mice with the natural context and immune variation found in the wild. We find that easily assayed immune quantities are largely ineffective as predictors of lymphocyte composition, either on their own or with other covariates. Immunoglobulin G (IgG) concentration and neutrophil-lymphocyte ratio show the most promise as indicators of other immune traits, but their explanatory power is limited. Our results prescribe caution in inferring immune phenotypes beyond what is directly measured, but they do also highlight some potential paths forward for the development of proxy measures employable by ecoimmunologists.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular vesicles: an emerging tool for wild immunology. 细胞外囊泡：野生免疫学的新兴工具。

Discovery immunology Pub Date : 2024-06-24 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae011

Camila Espejo, Vanessa O Ezenwa

{"title":"Extracellular vesicles: an emerging tool for wild immunology.","authors":"Camila Espejo, Vanessa O Ezenwa","doi":"10.1093/discim/kyae011","DOIUrl":"10.1093/discim/kyae011","url":null,"abstract":"The immune system is crucial for defending organisms against pathogens and maintaining health. Traditionally, research in immunology has relied on laboratory animals to understand how the immune system works. However, there is increasing recognition that wild animals, due to their greater genetic diversity, lifespan, and environmental exposures, have much to contribute to basic and translational immunology. Unfortunately, logistical challenges associated with collecting and storing samples from wildlife, and the lack of commercially available species-specific reagents have hindered the advancement of immunological research on wild species. Extracellular vesicles (EVs) are cell-derived nanoparticles present in all body fluids and tissues of organisms spanning from bacteria to mammals. Human and lab animal studies indicate that EVs are involved in a range of immunological processes, and recent work shows that EVs may play similar roles in diverse wildlife species. Thus, EVs can expand the toolbox available for wild immunology research, helping to overcome some of the challenges associated with this work. In this paper, we explore the potential application of EVs to wild immunology. First, we review current understanding of EV biology across diverse organisms. Next, we discuss key insights into the immune system gained from research on EVs in human and laboratory animal models and highlight emerging evidence from wild species. Finally, we identify research themes in wild immunology that can immediately benefit from the study of EVs and describe practical considerations for using EVs in wildlife research.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback. 淡水三刺鱼免疫系统的月相生物节律

Discovery immunology Pub Date : 2024-05-25 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae007

Joseph A Jackson, Alexander Stewart, Joanne Cable

{"title":"Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback.","authors":"Joseph A Jackson, Alexander Stewart, Joanne Cable","doi":"10.1093/discim/kyae007","DOIUrl":"10.1093/discim/kyae007","url":null,"abstract":"Immune responses are widely accepted to be under circadian regulation via a molecular clock, with many practical consequences, but much less is known of how other biological rhythms could affect the immune system. In this study, we search for lunar rhythms (circalunar, circasemilunar, and circatidal cycles) in the immune expression of the recently marine-derived freshwater fish, the low-plate morph of the three-spined stickleback. We employed time series of immune expression (mRNA) measurements for 14 immune-associated genes, representing a variety of immunological pathways. Times series measurements were taken on fish populations in the wild, in seminatural outdoor mesocosms, and in the laboratory, according to sampling regimens originally designed to study circannual variation but with the additional potential to provide information about lunar variation. Our evidence best supported the existence of a very small endogenous tidal rhythm. This is consistent with previous suggestions of the existence of a primordial tidal endogenous clock, some elements of which may be conserved in animals evolving outside the marine environment.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adapting for success: T cell features at tissue sites 适应成功：组织部位的 T 细胞特征

Discovery immunology Pub Date : 2024-05-18 DOI: 10.1093/discim/kyae009

Philip P Ahern, Emily Gwyer Findlay

引用次数: 0

IL-21 conditions antigen-presenting human γδ T-cells to promote IL-10 expression in naïve and memory CD4⁺ T-cells. IL-21 可调节抗原递呈人 γδ T 细胞，促进幼稚和记忆 CD4+ T 细胞中 IL-10 的表达。

Discovery immunology Pub Date : 2024-05-13 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae008

Christopher J Tyler, Inva Hoti, Daniel D Griffiths, Simone M Cuff, Robert Andrews, Maximilian Keisker, Raya Ahmed, Hinrich P Hansen, James O Lindsay, Andrew J Stagg, Bernhard Moser, Neil E McCarthy, Matthias Eberl

{"title":"IL-21 conditions antigen-presenting human γδ T-cells to promote IL-10 expression in naïve and memory CD4+ T-cells.","authors":"Christopher J Tyler, Inva Hoti, Daniel D Griffiths, Simone M Cuff, Robert Andrews, Maximilian Keisker, Raya Ahmed, Hinrich P Hansen, James O Lindsay, Andrew J Stagg, Bernhard Moser, Neil E McCarthy, Matthias Eberl","doi":"10.1093/discim/kyae008","DOIUrl":"10.1093/discim/kyae008","url":null,"abstract":"Direct interaction between T-cells exerts a major influence on tissue immunity and inflammation across multiple body sites including the human gut, which is highly enriched in 'unconventional' lymphocytes such as γδ T-cells. We previously reported that microbial activation of human Vγ9/Vδ2+ γδ T-cells in the presence of the mucosal damage-associated cytokine IL-15 confers the ability to promote epithelial barrier defence, specifically via induction of IL-22 expression in conventional CD4+ T-cells. In the current report, we assessed whether other cytokines enriched in the gut milieu also functionally influence microbe-responsive Vγ9/Vδ2 T-cells. When cultured in the presence of IL-21, Vγ9/Vδ2 T-cells acquired the ability to induce expression of the immunoregulatory cytokine IL-10 in both naïve and memory CD4+ T-cells, at levels surpassing those induced by monocytes or monocyte-derived DCs. These findings identify an unexpected influence of IL-21 on Vγ9/Vδ2 T-cell modulation of CD4+ T-cell responses. Further analyses suggested a possible role for CD30L and/or CD40L reverse signalling in mediating IL-10 induction by IL-21 conditioned Vγ9/Vδ2 T-cells. Our findings indicate that the local microenvironment exerts a profound influence on Vγ9/Vδ2 T-cell responses to microbial challenge, leading to induction of distinct functional profiles among CD4+ T-cells that may influence inflammatory events at mucosal surfaces. Targeting these novel pathways may offer therapeutic benefit in disorders such as inflammatory bowel disease.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1. Treg和自我反应T细胞的谱系：老朋友HTLV-1的单细胞视角。

Discovery immunology Pub Date : 2024-05-13 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae006

Masahiro Ono, Yorifumi Satou

{"title":"Spectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1.","authors":"Masahiro Ono, Yorifumi Satou","doi":"10.1093/discim/kyae006","DOIUrl":"10.1093/discim/kyae006","url":null,"abstract":"Despite extensive regulatory T cell (Treg) research, fundamental questions on in vivo dynamics remain to be answered. The current study aims to dissect several interwoven concepts in Treg biology, highlighting the 'self-reactivity' of Treg and their counterparts, namely naturally-arising memory-phenotype T-cells, as a key mechanism to be exploited by a human retroviral infection. We propose the novel key concept, Periodic T cell receptor (TCR)-signalled T-cells, capturing self-reactivity in a quantifiable manner using the Nr4a3-Timer-of-cell-kinetics-and-activity (Tocky) technology. Periodic and brief TCR signals in self-reactive T-cells contrast with acute TCR signals during inflammation. Thus, we propose a new two-axis model for T-cell activation by the two types of TCR signals or antigen recognition, elucidating how Foxp3 expression and acute TCR signals actively regulate Periodic TCR-signalled T-cells. Next, we highlight an underappreciated branch of immunological research on Human T-cell Leukemia Virus type 1 (HTLV-1) that precedes Treg studies, illuminating the missing link between the viral infection, CD25, and Foxp3. Based on evidence by single-cell analysis, we show how the viral infection exploits the regulatory mechanisms for T-cell activation and suggests a potential role of periodic TCR signalling in infection and malignant transformation. In conclusion, the new perspectives and models in this study provide a working framework for investigating Treg within the self-reactive T-cell spectrum, expected to advance understanding of HTLV-1 infection, cancer, and immunotherapy strategies for these conditions.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated type-17 cytokines are present in Axial Spondyloarthritis stool 轴性脊柱关节炎粪便中 17 型细胞因子升高

Discovery immunology Pub Date : 2024-05-04 DOI: 10.1093/discim/kyae005

I. Brough, Kelsey Thompson, Ciara Latore, F. Penkava, Chelsea Regan, Claire F. Pearson, Hui Shi, A. Ridley, Davide Simone, Lilian Lam, S. Bullers, Caroline Moussa, Rachel Feeney, Mohammed Hussein Al-Mossawi, Fiona Powrie, Stephen Young, Curtis Huttenhower, P. Bowness

引用次数: 0

Gamma delta (γδ) T cells in the female reproductive tract: active participants or indifferent bystanders in reproductive success? 女性生殖道中的γδ（γδ）T 细胞：生殖成功的积极参与者还是冷漠的旁观者？

Discovery immunology Pub Date : 2024-04-26 DOI: 10.1093/discim/kyae004

K. Foyle, Sarah A. Robertson

{"title":"Gamma delta (γδ) T cells in the female reproductive tract: active participants or indifferent bystanders in reproductive success?","authors":"K. Foyle, Sarah A. Robertson","doi":"10.1093/discim/kyae004","DOIUrl":"https://doi.org/10.1093/discim/kyae004","url":null,"abstract":"\u0000 The female reproductive tract accommodates and balances the unique immunological challenges of protection from sexually-transmitted pathogens and tolerance of the fetus and placenta in pregnancy. Leukocytes in the female reproductive tract actively engage in extensive maternal adaptations that are imperative for embryo implantation, placental development, and fetal support. γδ T cells are abundant at many mucosal sites in the body, where they provide protection against pathogens and cancer and have roles in tissue renewal and homeostasis. In this review we summarize studies in human and rodents showing that γδ T cells are prevalent in the female reproductive tract and fluctuate in response to hormone changes over the course of the cycle. Emerging evidence points to a link between changes in their abundance and molecular repertoire in the uterus and pregnancy disorders including recurrent miscarriage and preterm birth. However, defining the precise functional role of female reproductive tract γδ T cells and understanding their physiological significance in reproduction and pregnancy has remained elusive. Here, we critically analyze whether reproductive tract γδ T cells could be active participants in reproductive events - or alternatively whether their principal function is immune defense, in which case they may compromise pregnancy success unless adequately regulated.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0