Mucosal Immunology最新文献

{"title":"FcαRI (CD89) is upregulated on subsets of mucosal and circulating NK cells and regulates IgA-class specific signaling and functions","authors":"","doi":"10.1016/j.mucimm.2024.04.003","DOIUrl":"10.1016/j.mucimm.2024.04.003","url":null,"abstract":"<div><p>Immunoglobulin A (IgA) is the predominant mucosal antibody class with both anti- and pro-inflammatory roles<span><span>1</span></span>, <span><span>2</span></span>, <span><span>3</span></span>. However, the specific role of the IgA receptor cluster of differentiation (CD)89, expressed by a subset of natural killer (NK) cells, is poorly explored. We found that CD89 protein expression on circulating NK cells is infrequent in humans and rhesus macaques, but transcriptomic analysis showed ubiquitous CD89 expression, suggesting an inducible phenotype. Interestingly, CD89⁺ NK cells were more frequent in cord blood and mucosae, indicating a putative IgA-mediated NK cell function in the mucosae and infant immune system. CD89⁺ NK cells signaled through upregulated CD3 zeta chain (CD3ζ), spleen tyrosine kinase (Syk), zeta chain-associated protein kinase 70 (ZAP70), and signaling lymphocytic activation molecule family 1 (SLAMF1), but also showed high expression of inhibitory receptors such as killer cell lectin-like receptor subfamily G (KLRG1) and reduced activating NKp46 and NKp30. CD89-based activation or antibody-mediated cellular cytotoxicity with monomeric IgA1 reduced NK cell functions, while antibody-mediated cellular cytotoxicity with combinations of IgG and IgA2 was enhanced compared to IgG alone. These data suggest that functional CD89⁺ NK cells survey mucosal sites, but CD89 likely serves as regulatory receptor which can be further modulated depending on IgA and IgG subclass. Although the full functional niche of CD89⁺ NK cells remains unexplored, these intriguing data suggest the CD89 axis could represent a novel immunotherapeutic target in the mucosae or early life.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 692-699"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000400/pdfft?md5=9a26af4ee3c7eb7c3872443e32ea46e1&pid=1-s2.0-S1933021924000400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140767876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAdCAM-1 co-stimulation combined with retinoic acid and TGF-β induces blood CD8+ T cells to adopt a gut CD101+ TRM phenotype","authors":"","doi":"10.1016/j.mucimm.2024.04.004","DOIUrl":"10.1016/j.mucimm.2024.04.004","url":null,"abstract":"<div><p>Resident memory T cells (T_RMs) help control local immune homeostasis and contribute to tissue-protective immune responses. The local cues that guide their differentiation and localization are poorly defined. We demonstrate that mucosal vascular addressin cell adhesion molecule 1, a ligand for the gut-homing receptor α₄β₇ integrin, in the presence of retinoic acid and transforming growth factor-β (TGF-β) provides a co-stimulatory signal that induces blood cluster of differentiation (CD8⁺ T cells to adopt a T_RM-like phenotype. These cells express CD103 (integrin α_E) and CD69, the two major T_RM cell-surface markers, along with CD101. They also express C-C motif chemokine receptors 5 (CCR5) , C-C motif chemokine receptors 9 (CCR9), and α₄β₇, three receptors associated with gut homing. A subset also expresses E-cadherin, a ligand for α_Eβ₇. Fluorescent lifetime imaging indicated an α_Eβ₇ and E-cadherin cis interaction on the plasma membrane. This report advances our understanding of the signals that drive the differentiation of CD8⁺ T cells into resident memory T cells and provides a means to expand these cells <em>in vitro</em>, thereby affording an avenue to generate more effective tissue-specific immunotherapies.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 700-712"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000412/pdfft?md5=1de529852561125ba412d56f2a7634d4&pid=1-s2.0-S1933021924000412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TL1A priming induces a multi-cytokine Th9 cell phenotype that promotes robust allergic inflammation in murine models of asthma","authors":"","doi":"10.1016/j.mucimm.2024.03.006","DOIUrl":"10.1016/j.mucimm.2024.03.006","url":null,"abstract":"<div><p>Multi-cytokine-producing Th9 cells secrete IL-9 and type 2 cytokines and mediate mouse and human allergic inflammation. However, the cytokines that promote a multi-cytokine secreting phenotype have not been defined. Tumor necrosis factor superfamily member TL1A signals through its receptor DR3 to increase IL-9. Here we demonstrate that TL1A increases expression of IL-9 and IL-13 co-expressing cells in murine Th9 cell cultures, inducing a multi-cytokine phenotype. Mechanistically, this is linked to histone modifications allowing for increased accessibility at the <em>Il9</em> and <em>Il13</em> loci. We further show that TL1A alters the transcription factor network underlying expression of IL-9 and IL-13 in Th9 cells and increases binding of transcription factors to <em>Il9</em> and <em>Il13</em> loci. TL1A-priming enhances the pathogenicity of Th9 cells in murine models of allergic airway disease through the increased expression of IL-9 and IL-13. Lastly, in both chronic and memory-recall models of allergic airway disease, blockade of TL1A signaling decreases the multi-cytokine Th9 cell population and attenuates the allergic phenotype. Taken together, these data demonstrate that TL1A promotes the development of multi-cytokine Th9 cells that drive allergic airway diseases and that targeting pathogenic T helper cell-promoting cytokines could be an effective approach for modifying disease.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 537-553"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000254/pdfft?md5=213d4456140ec8261d3d9365e88b7886&pid=1-s2.0-S1933021924000254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ETS translocation variant 5 (ETV5) promotes CD4+ T cell–mediated intestinal inflammation and fibrosis in inflammatory bowel diseases","authors":"","doi":"10.1016/j.mucimm.2024.03.010","DOIUrl":"10.1016/j.mucimm.2024.03.010","url":null,"abstract":"<div><p>E26 transformation-specific translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the exact roles of ETV5 in regulating CD4⁺ T cell–mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced interleukin (IL)-9 and its transcription factor IRF4 expression in IBD CD4⁺ T cells under T helper type 9 (Th9) cells–polarizing conditions. The silencing of IRF4 inhibited ETV5-induced IL-9 expression. CD4⁺ T cell–specific ETV5 deletion ameliorated intestinal inflammation and fibrosis in trinitrobenzene sulfonic acid (TNBS)–induced experimental colitis and CD4⁺ T cell–transferred recombination-activating gene-1 knockout (Rag1^−/−) colitis mice, characterized by less CD4⁺ T cell infiltration and lower fibroblast activation and collagen deposition in the colonic tissues. Furthermore, IL-9 treatment aggressive TNBS–induced intestinal fibrosis in CD4⁺ T cell–specific ETV5 deletion and wild-type control mice. <em>In vitro</em>, human intestinal fibroblasts cocultured with ETV5 overexpressed-Th9 cells expressed higher levels of collagen I and III, whereas an inclusion of anti-IL-9 antibody could reverse this effect. Ribonucleic acid sequencing analysis demonstrated that IL-9 upregulated TAF1 expression in human intestinal fibroblasts. Clinical data showed that number of α-smooth muscle actin⁺TAF1⁺ fibroblasts are higher in inflamed mucosa of patients with IBD. Importantly, TAF1 small interfering ribonucleic acid treatment suppressed IL-9–mediated profibrotic effect <em>in vitro</em>. These findings reveal that CD4⁺ T cell–derived ETV5 promotes intestinal inflammation and fibrosis through upregulating IL-9–mediated intestinal inflammatory and fibrotic response in IBD. Thus, the ETV5/IL-9 signal pathway in T cells might represent a novel therapeutic target for intestinal inflammation and fibrosis in IBD.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 584-598"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000308/pdfft?md5=fee9b986ce3d09219e662f20c28dd077&pid=1-s2.0-S1933021924000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formyl peptide receptor 1 mitigates colon inflammation and maintains mucosal homeostasis through the inhibition of CREB-C/EBPβ-S100a8 signaling","authors":"","doi":"10.1016/j.mucimm.2024.04.001","DOIUrl":"10.1016/j.mucimm.2024.04.001","url":null,"abstract":"<div><p>Excessive inflammatory responses are the main characteristic of ulcerative colitis (UC). Activation of formyl peptide receptor 1 (FPR1) has been found to promote the proliferation and migration of epithelial cells, but its role and therapeutic potential in UC remain unclear. This study observed an increased expression of FPR1 in a mouse model of colitis. Interestingly, FPR1 deficiency exacerbated UC and increased the secretion of the proinflammatory mediator from immune cells (e.g. macrophages), S100a8, a member of the damage-associated molecular patterns. Notably, the administration of the FPR agonist Cmpd43 ameliorated colon injury in a preclinical mice model of UC, likely via inhibiting phosphorylation of cyclic adenosine monophosphate-response element-binding protein and expression of CCAAT/enhancer-binding protein β, which in turn suppressed the secretion of S100a8. In conclusion, these findings discovered a novel role of FPR1 in the development of colitis and will facilitate the development of FPR1-based pharmacotherapy to treat UC.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 651-672"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000382/pdfft?md5=f3362024fc9b37f17305d0fe3a33ab74&pid=1-s2.0-S1933021924000382-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140777323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ileal mucus viscoelastic properties differ in Crohn’s disease","authors":"","doi":"10.1016/j.mucimm.2024.05.002","DOIUrl":"10.1016/j.mucimm.2024.05.002","url":null,"abstract":"<div><p>Crohn's disease (CD) is an inflammatory bowel disease that can affect any part of the gastrointestinal tract, frequently involving the terminal ileum. While colonic mucus alterations in CD patients have been described, terminal ileal mucus and its mechanobiological properties have been neglected. Our study is the first of its kind to decipher the viscoelastic and network properties of ileal mucus. With that aim, oscillatory rheological shear measurements based on an airway mucus protocol that was thoroughly validated for ileal mucus were performed. Our pilot study analyzed terminal ileum mucus from controls (<em>n</em> = 14) and CD patients (<em>n</em> = 14). Mucus network structure was visualized by scanning electron microscopy. Interestingly, a statistically significant increase in viscoelasticity as well as a decrease in mesh size was observed in ileal mucus from CD patients compared to controls. Furthermore, rheological data were analyzed in relation to study participants’ clinical characteristics, revealing a noteworthy trend between non-smokers and smokers. In conclusion, this study provides the first data on the viscoelastic properties and structure of human ileal mucus in the healthy state and Crohn’s disease, demonstrating significant alterations between groups and highlighting the need for further research on mucus and its effect on the underlying epithelial barrier.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 713-722"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000436/pdfft?md5=7552f17e4ce0fd8bc0360d25697985fe&pid=1-s2.0-S1933021924000436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LECs regulate neutrophil clearance through IL-17RC/CMTM4/NF-κB axis at sites of inflammation or infection","authors":"","doi":"10.1016/j.mucimm.2024.05.003","DOIUrl":"10.1016/j.mucimm.2024.05.003","url":null,"abstract":"<div><p>The lymphatic system plays a vital role in the regulation of tissue fluid balance and the immune response to inflammation or infection. The effects of lymphatic endothelial cells (LECs) on the regulation of neutrophil migration have not been well-studied. In three murine models: imiquimod-induced skin inflammation, <em>Staphylococcus aureus</em>-induced skin infection, and ligature-induced periodontitis, we show that numerous neutrophils migrate from inflamed or infected tissues to the draining lymph nodes via lymphatic vessels. Moreover, inflamed or infected tissues express a high level of interleukin (IL)-17A and tumor necrosis factor (TNF)-α, simultaneously with a significant increase in the release of neutrophil attractors, including CXCL1, CXCL2, CXCL3, and CXCL5. Importantly, <em>in vitro</em> stimulation of LECs with IL-17A plus TNF-α synergistically promoted these chemokine secretions. Mechanistically, tetra-transmembrane protein CMTM4 directly binds to IL-17RC in LECs. IL-17A plus TNF-α stimulates CXC chemokine secretion by promoting nuclear factor-kappa B signaling. In contrast, knockdown of CMTM4 abrogates IL-17A plus TNF-α activated nuclear factor-kappa B signaling pathways. Lastly, the local administration of adeno-associated virus for CMTM4 in Prox1-CreER^T2 mice, mediating LEC-specific overexpression of CMTM4, promotes the drainage of neutrophils by LECs and alleviates immune pathological responses. Thus, our findings reveal the vital role of LECs-mediated neutrophil attraction and clearance at sites of inflammation or infection.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 723-738"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000448/pdfft?md5=4852460cedca06f516f12ffd936c9ef8&pid=1-s2.0-S1933021924000448-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity","authors":"","doi":"10.1016/j.mucimm.2024.03.013","DOIUrl":"10.1016/j.mucimm.2024.03.013","url":null,"abstract":"<div><p>Intestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these responses remain poorly understood. Interferon regulatory factors (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by epithelial cells, but its roles in IEC immunity are unknown. In this study, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screens found that <em>Irf6</em> deficiency enhanced IFN-stimulated antiviral responses in transformed mouse IECs but not macrophages. Furthermore, knockout (KO) of <em>Irf6</em> in IEC organoids resulted in profound changes to homeostasis and immunity gene expression. <em>Irf6</em> KO organoids grew more slowly, and single-cell ribonucleic acid sequencing indicated reduced expression of genes in epithelial differentiation and immunity pathways. IFN-stimulated gene expression was also significantly different in <em>Irf6</em> KO organoids, with increased expression of stress and apoptosis-associated genes. Functionally, the transcriptional changes in <em>Irf6</em> KO organoids were associated with increased cytotoxicity upon IFN treatment or inflammasome activation. These data indicate a previously unappreciated role for IRF6 in IEC biology, including regulation of epithelial development and moderation of innate immune responses to minimize cytotoxicity and maintain barrier function.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 633-650"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000321/pdfft?md5=c0535a80131eae17cddeb5a5feabac6a&pid=1-s2.0-S1933021924000321-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140800634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 Spike protein triggers gut impairment since mucosal barrier to innermost layers: From basic science to clinical relevance","authors":"","doi":"10.1016/j.mucimm.2024.03.009","DOIUrl":"10.1016/j.mucimm.2024.03.009","url":null,"abstract":"<div><p>Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, <em>in vitro</em> approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl⁻ secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1β, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 565-583"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000291/pdfft?md5=3b61945ffeb24251b400c856a1bf1d5b&pid=1-s2.0-S1933021924000291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The atypical IκB family member Bcl3 determines differentiation and fate of intestinal RORγt+ regulatory T-cell subsets","authors":"","doi":"10.1016/j.mucimm.2024.04.002","DOIUrl":"10.1016/j.mucimm.2024.04.002","url":null,"abstract":"<div><p>Peripherally-induced regulatory T cells (pTregs) expressing the retinoic acid receptor-related orphan-receptor gamma t (RORγt) are indispensable for intestinal immune homeostasis. Nuclear factor kappa family members regulate the differentiation of thymic Tregs and promote their survival in the periphery. However, the Treg intrinsic molecular mechanisms controlling the size of the pTregs in the intestine and associated lymphoid organs remain unclear. Here, we provide direct evidence that B-cell lymphoma 3 (Bcl3) limits the development of pTregs in a T cell-intrinsic manner. Moreover, the absence of Bcl3 allowed for the formation of an unusual intestinal Treg population co-expressing the transcription factors Helios and RORγt. The expanded RORγt⁺ Treg populations in the absence of Bcl3 displayed an activated phenotype and secreted high levels of the anti-inflammatory cytokines interleukin (IL)-10 and transforming growth factor beta. They were fully capable of suppressing effector T cells in a transfer colitis model despite an intrinsic bias to trans-differentiate toward T helper 17-like cells. Finally, we provide a Bcl3-dependent gene signature in pTregs including altered responsiveness to the cytokines IL-2, IL-6, and tumor necrosis factor alpha. Our results demonstrate that Bcl3 acts as a molecular switch to limit the expansion of different intestinal Treg subsets and may thus serve as a novel therapeutic target for inflammatory bowel disease by restoring intestinal immune tolerance.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 4","pages":"Pages 673-691"},"PeriodicalIF":7.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000394/pdfft?md5=393453ac16b69c21623f6d461d94b867&pid=1-s2.0-S1933021924000394-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140762834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}