Immunology最新文献

{"title":"Roles of Menin in T cell differentiation and function: Current knowledge and perspectives","authors":"Pingping Zhou,&nbsp;Weiru Liu,&nbsp;Jian Ma","doi":"10.1111/imm.13837","DOIUrl":"10.1111/imm.13837","url":null,"abstract":"<p>The commitment to specific T lymphocytes (T cell) lineages is governed by distinct transcription factors, whose expression is modulated through epigenetic mechanisms. Unravelling these epigenetic mechanisms that regulate T cell differentiation and function holds significant importance for understanding T cells. Menin, a multifunctional scaffolding protein, is implicated in various cellular processes, such as cell proliferation, cell cycle control, DNA repair and transcriptional regulation, primarily through epigenetic mechanisms. Existing research indicates Menin's impact on T cell differentiation and function, while a comprehensive and systematic review is currently lacking to consolidate these findings. In the current review, we have highlighted recent studies on the role of Menin in T cell differentiation and function, focusing mainly on its impact on the memory Th2 maintenance, Th17 differentiation and maintenance, CD4⁺ T cell senescence, and effector CD8⁺ T cell survival. Considering Menin's crucial function in maintaining effector T cell function, the potential of inhibiting Menin activity in mitigating inflammatory diseases associated with excessive T cell activation has also been emphasised.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"258-273"},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IBD functions as a double-edged sword for food allergy in BALB/c mice model","authors":"Bihua Chen,&nbsp;Yuhong Wu,&nbsp;Huan Wu,&nbsp;Jinyan Gao,&nbsp;Xuanyi Meng,&nbsp;Hongbing Chen","doi":"10.1111/imm.13833","DOIUrl":"10.1111/imm.13833","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) and food allergy (FA) increase in tandem, but the potential impact of IBD on FA remains unclear. We sought to determine the role of IBD on FA. We first assessed the changes of FA-related risk factors in dextran sulphate sodium salt (DSS) induced colitis mice model. Then, we evaluated the role of IBD on FA in mice. FA responses were determined using a clinical allergy score, body temperature change, serum antibody levels, cytokines level and mouse mast cell protease 1 (MMCP-1) concentration. Accumulation of regulatory T cells was tested using flow cytometry. Intestinal changes were identified by histology, immunohistochemistry, gene expression and gut microbial community structure. In DSS-induced colitis mice model, we found the intestinal damage, colonic neutrophil infiltration, and downregulation of splenic Th2 cytokines and Tregs in mesenteric lymph nodes (MLN). Moreover, we also found that IBD can alleviate the FA symptoms and lead to the significant downregulation of Th2 cytokines, serum IgE and MMCP-1. However, IBD exacerbates intestinal injury and promotes the gene expression levels of IL-33 and IL-5 in the small intestine, damages the intestinal tissue structure and aggravates intestinal dysbiosis in FA. IBD functions as a double-edged sword in FA. From the perspective of clinical symptoms and humoral immune responses, IBD can reduce FA response by downregulating Th2 cytokines. But from the perspective of the intestinal immune system, IBD potentially disrupts intestinal tolerance to food antigens by damaging intestinal tissue structure and causing intestinal dysbiosis.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"394-407"},"PeriodicalIF":4.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic TB control and the sequence of innate/adaptive immune responses to infection: MHC-II alleles determine the size of the S100A8/9-producing neutrophil population","authors":"Nadezhda Logunova,&nbsp;Marina Kapina,&nbsp;Alexander Dyatlov,&nbsp;Tatiana Kondratieva,&nbsp;Elvira Rubakova,&nbsp;Konstantin Majorov,&nbsp;Elena Kondratieva,&nbsp;Irina Linge,&nbsp;Alexander Apt","doi":"10.1111/imm.13836","DOIUrl":"10.1111/imm.13836","url":null,"abstract":"<p>Among several quantitative trait loci involved in tuberculosis (TB) control in mice, one was mapped within the chromosome 17 segment occupied by the <i>H2</i> complex and another within the chromosome 3 segment comprising the <i>S100A8/9</i> genes, which encode neutrophil inflammatory factor S100A8/9. Previously, we developed a panel of <i>H2</i>-congenic mouse strains differing by small segments of the major histocompatibility complex Class II (MHC-II) region from TB-susceptible <i>H2</i>^j mice transferred onto the genetic background of the TB-resistant C57BL/6 (<i>H2</i>^b) strain. Susceptible B6.I-9.3 mice differ from B6 progenitors by the alleles of their only classical MHC-II <i>H2-Aβ</i> gene. The goals of the present study were to: (i) comprehensively characterise the differences in TB-related phenotypes between mice of the two strains and (ii) decipher interactions between the <i>H2-Aβ</i> and <i>S100A8/9</i> genes. Here, we describe the dynamics of TB-related phenotypes differentiating B6.I-9.3 and B6 mice (colony forming units counts, histopathology, lung immune cell infiltration and cytokine profiles). We show that disproportionally diminished CD4⁺ T-cell population, an enlarged S100A8/9-positive neutrophil population and higher S100A8/9 serum levels in B6.I-9.3 mice collectively form the ‘susceptible’ phenotype before infection. An increase in IL-17 and a decrease in intrferon-gamma production by CD4⁺ T-cells in these mice provide a mechanistic explanation of this phenotype. Using F2 segregation analysis, we show that the number of S100A8/9-producing neutrophils in lungs and spleens and the proportion of Th17 CD4⁺ T-cells in lungs are significantly lower in the presence of the <i>MHC-II</i> dominant ‘resistant’ <i>b</i> allele compared to the recessive ‘susceptible’ <i>j/j</i> genotype. This provides direct genetic evidence that MHC-II-regulated CD4⁺ T-cell landscapes determine neutrophil abundance before infection, an important pathogenic factor in TB immunity.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"381-393"},"PeriodicalIF":4.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythropoietin induces tumour progression and CD39 expression on immune cells in a preclinical model of triple-negative breast cancer","authors":"Stéphanie Bessoles,&nbsp;Andrada Chiron,&nbsp;Guillaume Sarrabayrouse,&nbsp;Pierre De La Grange,&nbsp;Amine M. Abina,&nbsp;Salima Hacein-Bey-Abina","doi":"10.1111/imm.13832","DOIUrl":"10.1111/imm.13832","url":null,"abstract":"<p>The adverse effects observed in some cancer patients treated with erythropoiesis-stimulating agents such as erythropoietin (EPO) might be due to the latter's well-known immunosuppressive functions. Here, we used a mouse model of syngeneic triple-negative breast cancer to explore EPO's immunomodulatory role in a tumour setting. Our results showed that EPO treatment promotes tumour growth, exacerbates the ‘immune desert’, and results in a ‘cold tumour’. EPO treatment changed the immune cell distribution in peripheral blood, secondary lymphoid organs, and the tumour microenvironment (TME). Our in-depth analysis showed that EPO mainly impacts CD4 T cells by accelerating their activation in the spleen and thus their subsequent exhaustion in the TME. This process is accompanied by a general elevation of CD39 expression by several immune cells (notably CD4 T cells in the tumour and spleen), which promotes an immunosuppressive TME. Lastly, we identified a highly immunosuppressive CD39⁺ regulatory T cell population (ICOS⁺, CTLA4⁺, Ki67⁺) as a potential biomarker of the risk of EPO-induced tumour progression. EPO displays pleiotropic immunosuppressive functions and enhances mammary tumour progression in mice.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"360-380"},"PeriodicalIF":4.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions","authors":"Marianne Strazza,&nbsp;Ruijiang Song,&nbsp;Shannon Hiner,&nbsp;Adam Mor","doi":"10.1111/imm.13828","DOIUrl":"10.1111/imm.13828","url":null,"abstract":"<p>Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the ligand binding sites of stimulatory or inhibitory co-receptors. Blocking ligand binding prevents downstream signalling and modulates specific T cell functions. Since 1985, the FDA has approved over 100 monoclonal antibodies against immune receptors. This therapeutic approach significantly improved the care of patients with numerous immune-related conditions; however, many patients are unresponsive, and some develop immune-related adverse events. One reason for that is the lack of consideration for the localization of these receptors on the cell surface of the immune cells in the context of the immune synapse. In addition to blocking ligand binding, changing the location of these receptors on the cell surface within the different compartments of the immunological synapse could serve as an alternative, efficient, and safer approach to treating these patients. This review discusses the potential therapeutic advantages of altering proteins' localization within the immune synapse and summarizes published work in this field. It also discusses the novel use of bispecific antibodies to induce the clustering of receptors on the cell surface. It presents the rationale for developing novel antibodies, targeting the organization of signalling receptor complexes on the cell surface. This approach offers an innovative and emerging technology to treat cancer patients resistant to current immunotherapies.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"248-257"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCK2 maintains intestinal homeostasis and prevents colitis by protecting antibody-secreting cells from oxidative stress","authors":"Kun-Long Duan,&nbsp;Tian-Xiang Wang,&nbsp;Jian-Wei You,&nbsp;Hai-Ning Wang,&nbsp;Zhi-Qiang Wang,&nbsp;Zi-Xuan Huang,&nbsp;Jin-Ye Zhang,&nbsp;Yi-Ping Sun,&nbsp;Yue Xiong,&nbsp;Kun-Liang Guan,&nbsp;Dan Ye,&nbsp;Li Chen,&nbsp;Ronghua Liu,&nbsp;Hai-Xin Yuan","doi":"10.1111/imm.13827","DOIUrl":"10.1111/imm.13827","url":null,"abstract":"<p>Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"339-359"},"PeriodicalIF":4.9,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A detective story of intermittent fasting effect on immunity","authors":"Ru-xue Ma","doi":"10.1111/imm.13829","DOIUrl":"10.1111/imm.13829","url":null,"abstract":"<p>Intermittent fasting (IF) refers to periodic fasting routines, that caloric intake is minimized not by meal portion size reduction but by intermittently eliminating ingestion of one or several consecutive meals. IF can instigate comprehensive and multifaceted alterations in energy metabolism, these metabolic channels may aboundingly function as primordial mechanisms that interface with the immune system, instigating intricate immune transformations. This review delivers a comprehensive understanding of IF, paying particular attention to its influence on the immune system, thus seeking to bridge these two research domains. We explore how IF effects lipid metabolism, hormonal levels, circadian rhythm, autophagy, oxidative stress, gut microbiota, and intestinal barrier integrity, and conjecture about the mechanisms orchestrating the intersect between these factors and the immune system. Moreover, the review includes research findings on the implications of IF on the immune system and patients burdened with autoimmune diseases.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"227-247"},"PeriodicalIF":4.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell”","authors":"","doi":"10.1111/imm.13830","DOIUrl":"10.1111/imm.13830","url":null,"abstract":"<p>Liu X, Xu X, Liao Y, Yao W, Geng X, Zeng X, et al. Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell. Immunology. 2024;172(2):210–25. https://doi.org/10.1111/imm.13767.</p><p>Authors checked the data of the paper recently and found that Figure 2b is unnecessary. While the old Figure 2b describes a portion of the same data, which are described in Figure 2a. It is unnecessary to repeatedly present these data. Thus, authors removed the old Figure 2b from fig. 1._</p><p>We apologise for this error.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"669-670"},"PeriodicalIF":4.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of different functions of CD8+ T cell subpopulations by a novel monoclonal antibody","authors":"Kantinan Chuensirikulchai,&nbsp;Supansa Pata,&nbsp;Witida Laopajon,&nbsp;Nuchjira Takheaw,&nbsp;Kamonporn Kotemul,&nbsp;Kanyaruck Jindaphun,&nbsp;Saichit Khummuang,&nbsp;Watchara Kasinrerk","doi":"10.1111/imm.13826","DOIUrl":"10.1111/imm.13826","url":null,"abstract":"<p>The explicit identification of CD8⁺ T cell subpopulation is important for deciphering the role of CD8⁺ T cells for protecting our body against invading pathogens and cancer. Our generated monoclonal antibody (mAb), named FE-1H10, recognized two novel subpopulations of peripheral blood CD8⁺ T cells, FE-1H10⁺ and FE-1H10⁻ CD8⁺ T cells. The molecule recognized by mAb FE-1H10 (FE-1H10 molecules) had a higher distribution on effector memory CD8⁺ T cell subsets. The functions of FE-1H10⁻ and FE-1H10⁺ CD8⁺ T cells were investigated. T cell proliferation assays revealed that FE-1H10⁻ CD8⁺ T cells exhibited a higher proliferation rate than FE-1H10⁺ CD8⁺ T cells, whereas FE-1H10⁺ CD8⁺ T cells produced higher levels of IFN-γ and TNF-α than FE-1H10⁻ CD8⁺ T cells. In T cell cytotoxicity assays, FE-1H10⁺ CD8⁺ T cells were able to kill target cells better than FE-1H10⁻ CD8⁺ T cells. RNA-sequencing analysis confirmed that these subpopulations were distinct: FE-1H10⁺ CD8⁺ T cells have higher expression of genes involved in effector functions (<i>IFNG</i>, <i>TNF</i>, <i>GZMB</i>, <i>PRF1</i>, <i>GNLY</i>, <i>FASL</i>, <i>CX3CR1</i>) while FE-1H10⁻ CD8⁺ T cells have greater expression of genes related to memory CD8⁺ T cell populations (<i>CCR7</i>, <i>SELL</i>, <i>TCF7</i>, <i>CD40LG</i>). The results suggested that mAb FE-1H10 identifies two novel distinctive CD8⁺ T cell subpopulations. The FE-1H10⁺ CD8⁺ T cells carried a superior functionality in response to tumour cells. The uncover of these novel CD8⁺ T cell subpopulations may be the basis knowledge of an optional immunotherapy for the selection of potential CD8⁺ T cells in cancer treatment.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"321-338"},"PeriodicalIF":4.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition","authors":"Alejandra García-Torre,&nbsp;Eva Bueno-García,&nbsp;Marco A. Moro-García,&nbsp;Rocío López-Martínez,&nbsp;Beatriz Rioseras,&nbsp;Beatriz Díaz-Molina,&nbsp;José Luis Lambert,&nbsp;Rebeca Alonso-Arias","doi":"10.1111/imm.13824","DOIUrl":"10.1111/imm.13824","url":null,"abstract":"<p>Expansion of CD4⁺CD28^null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4⁺CD28^null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4⁺CD28^null T-lymphocytes than those with a ratio &lt;1. In vitro, IL-10 reduced the frequency of proliferative CD4⁺CD28^null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4⁺CD28^null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4⁺CD28^null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4⁺CD28^null T-lymphocytes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"296-309"},"PeriodicalIF":4.9,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}