Discovery immunology最新文献_第2页

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":"3 1","pages":"kyae008"},"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":"3 1","pages":"kyae006"},"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":"2 5","pages":""},"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

The ontogenesis and heterogeneity of basophils 嗜碱性粒细胞的本体形成和异质性

Discovery immunology Pub Date : 2024-02-02 DOI: 10.1093/discim/kyae003

Jiyeon Park, Suk-Jo Kang

{"title":"The ontogenesis and heterogeneity of basophils","authors":"Jiyeon Park, Suk-Jo Kang","doi":"10.1093/discim/kyae003","DOIUrl":"https://doi.org/10.1093/discim/kyae003","url":null,"abstract":"\u0000 Basophils are the rarest leukocytes, but they have essential roles in protection against helminths, allergic disorders, autoimmune diseases, and some cancers. For years, the clinical significance of basophils has been neglected because of the lack of proper experimental tools to study them. The development of basophil-specific antibodies and animal models, along with genomic advances like single-cell transcriptomics, has greatly enhanced our understanding of basophil biology. Recent discoveries regarding basophils prompted us to write this review, emphasizing the basophil developmental pathway. In it, we chronologically examine the steps of basophil development in various species, which reveals the apparent advent of basophils predating IgE and basophil’s IgE-independent regulatory role in primitive vertebrates. Then, we cover studies of basophil development in adult bone marrow, and compare those of murine and human basophils, introducing newly identified basophil progenitors and mature basophil subsets, as well as the transcription factors that regulate the transitions between them. Last, we discuss the heterogeneity of tissue-resident basophils, which may develop through extramedullary hematopoiesis. We expect that this review will contribute to a deeper understanding of basophil biology from the intricate aspects of basophil development and differentiation, offering valuable insights for both researchers and clinicians.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"247 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139809575","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

The ontogenesis and heterogeneity of basophils 嗜碱性粒细胞的本体形成和异质性

Discovery immunology Pub Date : 2024-02-02 DOI: 10.1093/discim/kyae003

Jiyeon Park, Suk-Jo Kang

{"title":"The ontogenesis and heterogeneity of basophils","authors":"Jiyeon Park, Suk-Jo Kang","doi":"10.1093/discim/kyae003","DOIUrl":"https://doi.org/10.1093/discim/kyae003","url":null,"abstract":"\u0000 Basophils are the rarest leukocytes, but they have essential roles in protection against helminths, allergic disorders, autoimmune diseases, and some cancers. For years, the clinical significance of basophils has been neglected because of the lack of proper experimental tools to study them. The development of basophil-specific antibodies and animal models, along with genomic advances like single-cell transcriptomics, has greatly enhanced our understanding of basophil biology. Recent discoveries regarding basophils prompted us to write this review, emphasizing the basophil developmental pathway. In it, we chronologically examine the steps of basophil development in various species, which reveals the apparent advent of basophils predating IgE and basophil’s IgE-independent regulatory role in primitive vertebrates. Then, we cover studies of basophil development in adult bone marrow, and compare those of murine and human basophils, introducing newly identified basophil progenitors and mature basophil subsets, as well as the transcription factors that regulate the transitions between them. Last, we discuss the heterogeneity of tissue-resident basophils, which may develop through extramedullary hematopoiesis. We expect that this review will contribute to a deeper understanding of basophil biology from the intricate aspects of basophil development and differentiation, offering valuable insights for both researchers and clinicians.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139869558","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

Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes. 驱动白细胞介素-15 对组织淋巴细胞产生平衡和炎症效应的信号机制。

Discovery immunology Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae002

Neema Skariah, Olivia J James, Mahima Swamy

{"title":"Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes.","authors":"Neema Skariah, Olivia J James, Mahima Swamy","doi":"10.1093/discim/kyae002","DOIUrl":"10.1093/discim/kyae002","url":null,"abstract":"There is an intriguing dichotomy in the function of cytokine interleukin-15-at low levels, it is required for the homeostasis of the immune system, yet when it is upregulated in response to pathogenic infections or in autoimmunity, IL-15 drives inflammation. IL-15 associates with the IL-15Rα within both myeloid and non-haematopoietic cells, where IL-15Rα trans-presents IL-15 in a membrane-bound form to neighboring cells. Alongside homeostatic maintenance of select lymphocyte populations such as NK cells and tissue-resident T cells, when upregulated, IL-15 also promotes inflammatory outcomes by driving effector function and cytotoxicity in NK cells and T cells. As chronic over-expression of IL-15 can lead to autoimmunity, IL-15 expression is tightly regulated. Thus, blocking dysregulated IL-15 and its downstream signalling pathways are avenues for immunotherapy. In this review we discuss the molecular pathways involved in IL-15 signalling and how these pathways contribute to both homeostatic and inflammatory functions in IL-15-dependent mature lymphoid populations, focusing on innate, and innate-like lymphocytes in tissues.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"3 1","pages":"kyae002"},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974799","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

Deciphering the relationship between temperature and immunity 解读温度与免疫力之间的关系

Discovery immunology Pub Date : 2024-01-30 DOI: 10.1093/discim/kyae001

Elizabeth Maloney, Darragh Duffy

{"title":"Deciphering the relationship between temperature and immunity","authors":"Elizabeth Maloney, Darragh Duffy","doi":"10.1093/discim/kyae001","DOIUrl":"https://doi.org/10.1093/discim/kyae001","url":null,"abstract":"Summary Fever is a hallmark symptom of disease across the animal kingdom. Yet, despite the evidence linking temperature fluctuation and immune response, much remains to be discovered about the molecular mechanisms governing these interactions. In patients with rheumatoid arthritis, for instance, it is clinically accepted that joint temperature can predict disease progression. But it was only recently demonstrated that the mitochondria of stimulated T cells can rise to an extreme 50°C, potentially indicating a cellular source of these localized ‘fevers’. A challenge to dissecting these mechanisms is a bidirectional interplay between temperature and immunity. Heat shock response is found in virtually all organisms, activating protective pathways when cells are exposed to elevated temperatures. However, the temperature threshold that activates these pathways can vary within the same organism, with human immune cells, in particular, demonstrating differential sensitivity to heat. Such inter-cellular variation may be clinically relevant given the small but significant temperature differences seen between tissues, ages, and sexes. Greater understanding of how such small temperature perturbations mediate immune responses may provide new explanations for persistent questions in disease such as sex disparity in disease prevalence. Notably, the prevalence and severity of many maladies are rising with climate change, suggesting temperature fluctuations can interact with disease on multiple levels. As global temperatures are rising, and our body temperatures are falling, questions regarding temperature–immune interactions are increasingly critical. Here, we review this aspect of environmental interplay to better understand temperature’s role in immune variation and subsequent risk of disease.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"94 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140480783","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

The effect of abatacept on T cell activation is not long-lived in vivo 阿帕他赛对体内 T 细胞活化的影响并不持久

Discovery immunology Pub Date : 2024-01-04 DOI: 10.1093/discim/kyad029

Larissa C da Rosa, H. Scales, R. Benson, James M Brewer, Iain B. McInnes, P. Garside

引用次数: 0

Optimising a linear ‘Doggybone’ DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen 通过加入 DNA 靶向序列和神经氨酸酶抗原优化流感病毒线性 "Doggybone "DNA 疫苗

Discovery immunology Pub Date : 2024-01-03 DOI: 10.1093/discim/kyad030

Robert F. Cunliffe, David C. Stirling, Ilaria Razzano, Valarmathy Murugaiah, E. Montomoli, Sungwon Kim, Madina Wane, Helen Horton, Lisa J. Caproni, J. Tregoning

{"title":"Optimising a linear ‘Doggybone’ DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen","authors":"Robert F. Cunliffe, David C. Stirling, Ilaria Razzano, Valarmathy Murugaiah, E. Montomoli, Sungwon Kim, Madina Wane, Helen Horton, Lisa J. Caproni, J. Tregoning","doi":"10.1093/discim/kyad030","DOIUrl":"https://doi.org/10.1093/discim/kyad030","url":null,"abstract":"\u0000 Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realise their potential. Here we investigate influenza virus vaccines made using a closed loop linear DNA platform, Doggybone™ DNA (dbDNA), produced by a rapid and scalable cell-free method. Influenza vaccines have mostly focussed on Haemagglutinin (HA), but the inclusion of Neuraminidase (NA) may provide additional protection. Here we explored the potential of including NA in a dbDNA vaccine, looking at DNA optimisation, mechanism and breadth of protection. We showed that DNA targeting sequences (DTS) improved immune responses against HA but not NA. We explored whether NA vaccine induced protection against influenza virus infection was cell mediated but depletion of CD8 and NK cells made no impact, suggesting it was antibody mediated. This is reflected in restriction of protection only homologous strains of influenza virus. Importantly, we saw that including both HA and NA in a single combined vaccine did not dampen the immune response to either one. Overall, we show that linear dbDNA can induce an immune response against NA which may offer increased protection in instances of HA mismatch where NA remains more conserved.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"23 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139389539","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