Discovery immunology最新文献_第3页

The generation of senescent-like CD4+ EMRA T cells in T2D and their contribution to poor COVID-19 vaccine responses T2D 中衰老样 CD4+ EMRA T 细胞的生成及其对 COVID-19 疫苗应答不良的贡献

Discovery immunology Pub Date : 2023-11-28 DOI: 10.1093/discim/kyad026

C. Garrod-Ketchley, Laure Mourgue d'Algue, Katie Littlewood, Gillian Hood, Anne Worthington, Melanie Pattrick, Caroline Sutcliffe, Zoi Valla, Noorshad Joti, Udeshi Zalak, Amy Edwards, Sarah Finer, S. Henson

{"title":"The generation of senescent-like CD4+ EMRA T cells in T2D and their contribution to poor COVID-19 vaccine responses","authors":"C. Garrod-Ketchley, Laure Mourgue d'Algue, Katie Littlewood, Gillian Hood, Anne Worthington, Melanie Pattrick, Caroline Sutcliffe, Zoi Valla, Noorshad Joti, Udeshi Zalak, Amy Edwards, Sarah Finer, S. Henson","doi":"10.1093/discim/kyad026","DOIUrl":"https://doi.org/10.1093/discim/kyad026","url":null,"abstract":"CD4+ T cells are essential for protection from viral pathogens, such as SARS-CoV-2. However, an increase in the dysfunction CD4+ EMRA subset is likely to hinder the immune response towards viruses. We show here that CD4+ EMRAs are increased with elevated blood glucose, such as people living with T2D, which alters mitochondrial function and causes the differentiation of CD4+ T cells, reducing the immune response to COVID-19 vaccination. CD4+ T cells were examined for senescence, their insulin dynamics, and mitochondrial function after in vitro culture of high and low glucose media, with or without rotenone or mitoQ. Serum samples were used to assess circulating inflammation and IgG antibodies to SARS-CoV-2. People living with T2D had increased expression of CD4+ EMRA T cells, the appearance of which correlated with increasing blood glucose values. The T2D cohort showed a reduced mitochondrial membrane potential and increased mtROS production. These results were mimicked using high glucose media which accelerated CD4+ T cell differentiation and reduced MMP. People living with T2D (non-hyperglycaemic and hyperglycaemic) had altered expression of inflammatory mediators. CD4+ EMRA cells did not respond to COVID-19 peptides, and people with T2D had a reduced T cell and antibody response to SARS-CoV-2 S1 spike protein. We have shown that senescent-like CD4+ EMRA influence the viral response in SARS-CoV-2 and that CD4+ EMRAs may arise from faulty mitochondrial dynamics due to increased environmental glucose. Further study is required to determine the direct link increased glucose has with CD4+ EMRA formation.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139216519","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

T cell and bacterial microbiota interaction at intestinal and skin epithelial interfaces 肠道和皮肤上皮界面的 T 细胞与细菌微生物群相互作用

Discovery immunology Pub Date : 2023-11-25 DOI: 10.1093/discim/kyad024

Damian Maseda, S. Manfredo-Vieira, Aimee S Payne

引用次数: 0

Gut immune responses and evolution of the gut microbiome – a hypothesis 肠道免疫反应和肠道微生物群的进化--一个假设

Discovery immunology Pub Date : 2023-11-23 DOI: 10.1093/discim/kyad025

Marcus W. Viney, Louise Cheynel

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RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression RAM 在 T 细胞活化过程中上调，是 RNA 帽形成和基因表达所必需的

Discovery immunology Pub Date : 2023-11-17 DOI: 10.1093/discim/kyad021

Katarzyna Knop, C. Gómez-Moreira, Alison Galloway, Dimitrinka Ditsova, V. Cowling

引用次数: 0

Immunotherapy in the context of immune-specialized environment of brain metastases 脑转移瘤免疫特化环境下的免疫疗法

Discovery immunology Pub Date : 2023-11-16 DOI: 10.1093/discim/kyad023

F. James, M. Lorger

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Eosinophils in obesity and obesity-associated disorders 嗜酸性粒细胞在肥胖和肥胖相关疾病中的作用

Discovery immunology Pub Date : 2023-11-14 DOI: 10.1093/discim/kyad022

Yanan Hu, Svetoslav Chakarov

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Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus 心包,纵隔脂肪相关淋巴细胞簇在烷烃诱导的系统性红斑狼疮模型中被迅速激活

Discovery immunology Pub Date : 2023-09-25 DOI: 10.1093/discim/kyad017

Karolina Bentkowska, Alex Hardgrave, Nadia Iqbal, Laura Gresty, Bethany Marsden, Sheila Macharia, Lucy Jackson-Jones

{"title":"Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus","authors":"Karolina Bentkowska, Alex Hardgrave, Nadia Iqbal, Laura Gresty, Bethany Marsden, Sheila Macharia, Lucy Jackson-Jones","doi":"10.1093/discim/kyad017","DOIUrl":"https://doi.org/10.1093/discim/kyad017","url":null,"abstract":"Abstract Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominated by auto-antibodies that recognise cellular components. Pleural involvement is the most common SLE-related lung disease. Natural antibodies are rapidly secreted by innate-like B cells following perturbation of homeostasis and are important in the early stages of immune activation. The serous cavities are home to large numbers of innate-like B cells present both within serous fluid and resident within fat-associated lymphoid clusters (FALCs). FALCs are important hubs for B-cell activation and local antibody secretion within the body cavities. Patients with SLE can develop anti-phospholipid antibodies and in rare situations develop alveolar haemorrhage. Utilising delivery of the hydrocarbon oil pristane in C57BL/6 mice as a model of SLE we identify a rapid expansion of pleural cavity B cells as early as day 3 after intra-peritoneal pristane delivery. Following pristane delivery, pericardial B1 B cells are proliferative, express the plasma-cell surface marker CD138 and secrete both innate and class switched antibodies highlighting that this cavity niche may play an unrecognised role in the initiation of lupus pleuritis.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135864884","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

Conventional and non-conventional antigen presentation by mast cells 肥大细胞的常规和非常规抗原呈递

Discovery immunology Pub Date : 2023-09-19 DOI: 10.1093/discim/kyad016

Chi-Ching Tung, Abhay P S Rathore, Ashley L St. John

引用次数: 0

Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection. 甲型流感病毒感染后先天性和适应性淋巴细胞产生IFNγ的三相性。

Discovery immunology Pub Date : 2023-08-19 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad014

George E Finney, Kerrie E Hargrave, Marieke Pingen, Thomas Purnell, David Todd, Freya MacDonald, Julie C Worrell, Megan K L MacLeod

{"title":"Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection.","authors":"George E Finney, Kerrie E Hargrave, Marieke Pingen, Thomas Purnell, David Todd, Freya MacDonald, Julie C Worrell, Megan K L MacLeod","doi":"10.1093/discim/kyad014","DOIUrl":"10.1093/discim/kyad014","url":null,"abstract":"Interferon gamma (IFNγ) is a potent antiviral cytokine that can be produced by many innate and adaptive immune cells during infection. Currently, our understanding of which cells produce IFNγ and where they are located at different stages of an infection is limited. We have used reporter mice to investigate in vivo expression of Ifnγ mRNA in the lung and secondary lymphoid organs during and following influenza A virus (IAV) infection. We observed a triphasic production of Ifnγ expression. Unconventional T cells and innate lymphoid cells, particularly NK cells, were the dominant producers of early Ifnγ, while CD4 and CD8 T cells were the main producers by day 10 post-infection. Following viral clearance, some memory CD4 and CD8 T cells continued to express Ifnγ in the lungs and draining lymph node. Interestingly, Ifnγ production by lymph node natural killer (NK), NKT, and innate lymphoid type 1 cells also continued to be above naïve levels, suggesting memory-like phenotypes for these cells. Analysis of the localization of Ifnγ+ memory CD4 and CD8 T cells demonstrated that cytokine+ T cells were located near airways and in the lung parenchyma. Following a second IAV challenge, lung IAV-specific CD8 T cells rapidly increased their expression of Ifnγ while CD4 T cells in the draining lymph node increased their Ifnγ response. Together, these data suggest that Ifnγ production fluctuates based on cellular source and location, both of which could impact subsequent immune responses.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad014"},"PeriodicalIF":0.0,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241613","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

CD56^bright natural killer cells preferentially kill proliferating CD4⁺ T cells. 具有 CD56 标记的自然杀伤细胞会优先杀死增殖的 CD4+ T 细胞。

Discovery immunology Pub Date : 2023-08-11 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad012

Mercede Lee, Charles J M Bell, Arcadio Rubio Garcia, Leila Godfrey, Marcin Pekalski, Linda S Wicker, John A Todd, Ricardo C Ferreira

{"title":"CD56bright natural killer cells preferentially kill proliferating CD4+ T cells.","authors":"Mercede Lee, Charles J M Bell, Arcadio Rubio Garcia, Leila Godfrey, Marcin Pekalski, Linda S Wicker, John A Todd, Ricardo C Ferreira","doi":"10.1093/discim/kyad012","DOIUrl":"10.1093/discim/kyad012","url":null,"abstract":"Human CD56br natural killer (NK) cells represent a small subset of CD56+ NK cells in circulation and are largely tissue-resident. The frequency and number of CD56br NK cells in blood has been shown to increase following administration of low-dose IL-2 (LD-IL2), a therapy aimed to specifically expand CD4+ regulatory T cells (Tregs). Given the potential clinical application of LD-IL-2 immunotherapy across several immune diseases, including the autoimmune disease type 1 diabetes, a better understanding of the functional consequences of this expansion is urgently needed. In this study, we developed an in vitro co-culture assay with activated CD4+ T cells to measure NK cell killing efficiency. We show that CD56br and CD56dim NK cells show similar efficiency at killing activated CD4+ conventional T (Tconv) and Treg cell subsets. However, in contrast to CD56dim cells, CD56br NK cells preferentially target highly proliferative cells. We hypothesize that CD56br NK cells have an immunoregulatory role through the elimination of proliferating autoreactive CD4+ Tconv cells that have escaped Treg suppression. These results have implications for the interpretation of current and future trials of LD-IL-2 by providing evidence for a new, possibly beneficial immunomodulatory mechanism of LD-IL-2-expanded CD56br NK cells.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad012"},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169103","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