Mucosal Immunology最新文献

{"title":"RelB and C/EBPα critically regulate the development of Peyer’s patch mononuclear phagocytes","authors":"Takashi Kanaya ,&nbsp;Toshi Jinnohara ,&nbsp;Sayuri Sakakibara ,&nbsp;Naoko Tachibana ,&nbsp;Takaharu Sasaki ,&nbsp;Tamotsu Kato ,&nbsp;Marc Riemann ,&nbsp;Jianshi Jin ,&nbsp;Katsuyuki Shiroguchi ,&nbsp;Eiryo Kawakami ,&nbsp;Hiroshi Ohno","doi":"10.1016/j.mucimm.2024.10.005","DOIUrl":"10.1016/j.mucimm.2024.10.005","url":null,"abstract":"<div><div>To establish protection against harmful foreign antigens, the small intestine harbors guardian sites called Peyer’s patches (PPs). PPs take up antigens through microfold (M) cells and transfer them to the sub-epithelial dome (SED), which contains a high density of mononuclear phagocytes (MPs), for T cell-priming. Accumulating evidence indicates that SED-MPs have unique functions other than T cell-priming to facilitate mucosal immune responses; however, the crucial factors regulating the functions of SED-MPs have not been determined. Here we performed transcriptome analysis, and identified the gene signatures of SED-MPs. Further data interpretation with transcription factor (TF) enrichment analysis estimated TFs responsible for the functions of SED-MPs. Among them, we found that RelB and C/EBPα were preferentially activated in SED-MPs. RelB-deficiency silenced the expression of IL-22BP and S100A4 by SED-MPs. On the other hand, C/EBPα-deficiency decreased the expression of lysozyme by SED-MPs, resulting the increased invasion of orally administered pathogenic bacteria into PPs and mesenteric lymph nodes. Our findings thus demonstrate that RelB and C/EBPα are essential to regulate the functions of SED-MPs.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 151-161"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470339","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":"Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis","authors":"Michael A. Schumacher ,&nbsp;Megan H. Thai ,&nbsp;Jonathan J. Hsieh ,&nbsp;Alexa Gramajo ,&nbsp;Cambrian Y. Liu ,&nbsp;Mark R. Frey","doi":"10.1016/j.mucimm.2024.11.007","DOIUrl":"10.1016/j.mucimm.2024.11.007","url":null,"abstract":"<div><div>Interleukin (IL)–33 is a key responder to intestinal injury and inflammation. In the colon, it is expressed by several cell populations, with the specific cellular source likely determining its role. The colonic epithelium expresses IL-33; however, the factors controlling its production and the specific epithelial lineage(s) expressing IL-33 are poorly understood. We recently reported that colonic epithelial IL-33 is induced by inhibition of glycogen synthase kinase-3β (GSK3β), but the signaling pathway mediating this induction is unknown. Here we tested the role of Wnt/β-catenin signaling in regulating colonic epithelial IL-33 at homeostasis and in injury-induced colitis. Transcriptomic analysis shows that epithelial IL-33 localizes to stem and progenitor cells. Ligand activation of Wnt/β-catenin signaling induced IL-33 in colonic organoid and cell cultures. Furthermore, small-molecule disruption of β-catenin interaction with cyclic AMP response element binding protein (CBP) prevented epithelial IL-33 induction. Antagonism of CBP/β-catenin signaling also prevented rapid epithelial IL-33 induction in dextran sodium sulfate (DSS)-mediated colitis, and was associated with maintenance of crypt-expressed host defense peptides. Together, these findings show β-catenin-driven production of epithelial IL-33 is an early response to colonic injury that shapes the crypt base defense response and suggest an immunoregulatory role for the stem cell niche in tissue injury.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 248-256"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730715","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":"Tear duct M cells exacerbate allergic conjunctivitis by facilitating germinal-center reactions.","authors":"Yuki Oya, Shunsuke Kimura, Maho Uemura, Yumiko Fujimura, Koji Hase","doi":"10.1016/j.mucimm.2025.01.009","DOIUrl":"10.1016/j.mucimm.2025.01.009","url":null,"abstract":"<p><p>The ocular mucosal surface regularly encounters external materials in the air and tear fluids. Microfold (M) cells, specialized epithelial cells for antigen uptake, are present in tear duct-associated lymphoid tissue (TALT) within the nasolacrimal sac; however, their immunological significance is unclear. We generated Krt5-Cre Tnfrsf11a^flox/flox mice, which lack functional M cells in the TALT, as evidenced by the absence of M-cell markers and reduced nanoparticle uptake. M cell deficiency resulted in fewer T follicular helper (Tfh) and germinal center (GC) B cells in the TALT under steady-state conditions. Upon induction of allergic conjunctivitis, control mice exhibited itching and increased Tfh and immunoglobulin E (IgE⁺) GC B cells in the TALT. However, M cell-deficient mice showed ameliorated allergic symptoms with fewer Tfh and IgE⁺ GC B cells. These findings suggest that M cells in TALT contribute to ocular surface immunosurveillance, whereas, upon allergen exposure, they play a critical role in the development of allergic conjunctivitis.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated myeloid differentiation in colitis is induced by inflammatory osteoclasts in a TNFα-dependent manner","authors":"Maria-Bernadette Madel ,&nbsp;Lidia Ibáñez ,&nbsp;Thomas Ciucci ,&nbsp;Julia Halper ,&nbsp;Antoine Boutin ,&nbsp;Ghada Beldi ,&nbsp;Alice C. Lavanant ,&nbsp;Henri-Jean Garchon ,&nbsp;Matthieu Rouleau ,&nbsp;Christopher G. Mueller ,&nbsp;Laurent Peyrin-Biroulet ,&nbsp;David Moulin ,&nbsp;Claudine Blin-Wakkach ,&nbsp;Abdelilah Wakkach","doi":"10.1016/j.mucimm.2024.09.005","DOIUrl":"10.1016/j.mucimm.2024.09.005","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is characterized by very severe intestinal inflammation associated with extra-intestinal manifestations. One of the most critical ones is bone destruction, which remains a major cause of morbidity and a risk factor for osteopenia and osteoporosis in IBD patients. In various mouse models of IBD, we and other have demonstrated concomitant bone loss due to a significant increase in osteoclast activity. Besides bone resorption, osteoclasts are known to control hematopoietic niches in vivo and modulate inflammatory responses in vitro, suggesting they may participate in chronic inflammation in vivo. Here, using different models of colitis, we showed that osteoclast inhibition significantly reduced disease severity and that induction of osteoclast differentiation by RANKL contributed to disease worsening. Our results demonstrate a direct link between osteoclast activity and myeloid cell accumulation in the intestine during colitis. RNAseq analysis of osteoclasts from colitic mice revealed overexpression of genes involved in the remodeling of hematopoietic stem cell niches. We also demonstrated that osteoclasts induced hematopoietic progenitor proliferation accompanied by a myeloid skewing in the early phases of colitis, which was confirmed in a model of RANKL-induced osteoclastogenesis. Mechanistically, inhibition of TNF-α reduced the induction of myeloid skewing by OCL both in vitro and in vivo. Lastly, we observed that osteoclastic activity and the proportion of myeloid cells in the blood are positively correlated in patients with Crohn’s disease. Collectively, our results shed light on a new role of osteoclasts in colitis in vivo, demonstrating they exert their colitogenic activity through an early action on hematopoiesis, leading to an increase in myelopoiesis sustaining gut inflammation.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 90-104"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350420","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":"MicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells","authors":"Luke B. Roberts ,&nbsp;Joana F. Neves ,&nbsp;Dave C.H. Lee ,&nbsp;Sara Valpione ,&nbsp;Roser Tachó-Piñot ,&nbsp;Jane K. Howard ,&nbsp;Matthew R. Hepworth ,&nbsp;Graham M. Lord","doi":"10.1016/j.mucimm.2024.09.001","DOIUrl":"10.1016/j.mucimm.2024.09.001","url":null,"abstract":"<div><div>The transcriptomic signatures that shape responses of innate lymphoid cells (ILCs) have been well characterised, however post-transcriptional mechanisms which regulate their development and activity remain poorly understood. We demonstrate that ILC groups of the intestinal lamina propria express mature forms of microRNA-142 (miR-142), an evolutionarily conserved microRNA family with several non-redundant regulatory roles within the immune system. Germline <em>Mir142</em> deletion alters intestinal ILC compositions, resulting in the absence of T-bet⁺ populations and significant defects in the cellularity and phenotypes of ILC3 subsets including CCR6⁺ LTi-like ILC3s. These effects were associated with decreased pathology in an innate-immune cell driven model of colitis. Furthermore, <em>Mir142^−/−</em> mice demonstrate defective development of gut-associated lymphoid tissues, including a complete absence of mature Peyer’s patches. Conditional deletion of <em>Mir142</em> in ILC3s (<em>Rorc</em>^Δ<em>^Mir142</em>) supported cell-intrinsic roles for these microRNAs in establishing or maintaining cellularity and functions of LTi-like ILC3s in intestinal associated tissues. RNAseq analysis revealed several target genes and biological pathways potentially regulated by miR-142 microRNAs in these cells. Finally, lack of <em>Mir142</em> in ILC3 led to elevated IL-17A production. These data broaden our understanding of immune system roles of miR-142 microRNAs, identifying these molecules as critical post-transcriptional regulators of ILC3s and intestinal mucosal immunity.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 39-52"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154591","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":"A reappraisal of IL-9 in inflammation and cancer","authors":"Fabian Bick ,&nbsp;Christophe Blanchetot ,&nbsp;Bart N. Lambrecht ,&nbsp;Martijn J. Schuijs","doi":"10.1016/j.mucimm.2024.10.003","DOIUrl":"10.1016/j.mucimm.2024.10.003","url":null,"abstract":"<div><div>While much is known about the functional effects of type 2 cytokines interleukin (IL)-4, IL-5 and IL-13 in homeostasis and disease, we still poorly understand the functions of IL-9. Chronic inflammation seen in allergic diseases, autoimmunity and cancer is however frequently accompanied by overproduction of this elusive type 2 cytokine. Initially identified as a T cell and mast cell growth factor, and later as the hallmark cytokine defining T_H9 cells, we now know that IL-9 is produced by multiple innate and adaptive immune cells. Recent evidence suggests that IL-9 controls discrete aspects of the allergic cascade, cellular responses of immune and stromal cells, cancer progression, tolerance and immune escape. Despite functioning as a pleiotropic cytokine in mucosal environments, like the lungs, the direct and indirect cellular targets of IL-9 are still not well characterized. Here, we discuss IL-9′s cellular senders and receivers, focusing on asthma and cancer. Moreover, we review current research directions and the outlook of targeted therapy centered around the biology of IL-9.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 1-15"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400786","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":"Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia","authors":"Laura Matarazzo ,&nbsp;Charlotte Costa ,&nbsp;Rémi Porte ,&nbsp;Jean-Michel Saliou ,&nbsp;Martin Figeac ,&nbsp;Fabien Delahaye ,&nbsp;Amélie Bonnefond ,&nbsp;Benoit Kloeckner ,&nbsp;Aymeric Silvin ,&nbsp;Florent Ginhoux ,&nbsp;Christelle Faveeuw ,&nbsp;Mara Baldry ,&nbsp;Christophe Carnoy ,&nbsp;Jean-Claude Sirard","doi":"10.1016/j.mucimm.2024.11.009","DOIUrl":"10.1016/j.mucimm.2024.11.009","url":null,"abstract":"<div><div>Host-directed therapy, using nasal administration of the Toll-like receptor 5 agonist flagellin in combination with antibiotics, has proven effective against pneumococcal pneumonia. In this study, we investigated the immune mechanisms underlying the therapy-induced protective effects. Transcriptomic analysis of lung tissue during infection revealed that flagellin not only enhanced pathways associated with myeloid cell infiltration into the airways and antimicrobial functions, but also promoted the early and transient mobilization of neutrophils and inflammatory monocytes. Neutrophils were identified as crucial for the protective effects of flagellin. The adjunct activity of flagellin correlated with the increased recruitment of neutrophils into airways, their localization at the periphery of bronchi, alveoli, and lung vessels, along with alterations in phagocytic activity. Clustering analysis identified seven neutrophil subsets; notably, flagellin adjunct treatment expanded clusters involved in recruitment and antibacterial activity, and primed augmented functionality. In conclusion, this study highlights specific neutrophil subsets as a promising target for host-directed therapy in infection.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 257-268"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730708","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":"Organismal mucosal immunology: A perspective through the eyes of game theory","authors":"Eduardo J. Villablanca","doi":"10.1016/j.mucimm.2024.12.003","DOIUrl":"10.1016/j.mucimm.2024.12.003","url":null,"abstract":"<div><div>In complex organisms, functional units must interact cohesively to maintain homeostasis, especially within mucosal barriers that house diverse, specialized cell exposed to constant environmental challenges. Understanding how homeostasis at mucosal barriers is maintained and how its disruption can lead to autoimmune diseases or cancer, requires a holistic view. Although omics approaches and systems immunology have become powerful tools, they are not without limitations; interpretations may reflect researchers’ assumptions, even if other explanations exist. In this perspective, I propose that applying game theory concepts to mucosal immunology could help interpret complex data, offering fresh perspectives and supporting the exploration of alternative scenarios. By framing the mucosal immune system as a network of strategic interactions with multiple possible outcomes, game theory, which analyzes strategic interactions and decision-making processes, could illuminate novel cell types and functions, cell interactions, and responses to pathogens and commensals, leading to a more comprehensive understanding of immune homeostasis and diseases. In addition, game theory might encourage researchers to consider a broader range of possibilities, reduce the risk of myopic thinking, and ultimately enable a more refined and comprehensive understanding of the complexity of the immune system at mucosal barriers. This perspective aims to introduce game theory as a complementary framework for mucosal immunologists, encouraging them to incorporate these concepts into data interpretation and system modeling.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 16-25"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822315","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":"Corrigendum to “Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway” [Mucosal Immunol. 17(3) (2024) 323–345]","authors":"Yunxia Xue ,&nbsp;Pengyang Xu ,&nbsp;Yu Hu ,&nbsp;Sijing Liu ,&nbsp;Ruyu Yan ,&nbsp;Shutong Liu ,&nbsp;Yan Li ,&nbsp;Jun Liu ,&nbsp;Ting Fu ,&nbsp;Zhijie Li","doi":"10.1016/j.mucimm.2025.01.001","DOIUrl":"10.1016/j.mucimm.2025.01.001","url":null,"abstract":"","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Page 269"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023979","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":"Card9 and MyD88 differentially regulate Th17 immunity to the commensal yeast Malassezia in the murine skin","authors":"Meret Tuor ,&nbsp;Mark H.T. Stappers ,&nbsp;Alice Desgardin ,&nbsp;Fiorella Ruchti ,&nbsp;Florian Sparber ,&nbsp;Selinda J. Orr ,&nbsp;Neil A.R. Gow ,&nbsp;Salomé LeibundGut-Landmann","doi":"10.1016/j.mucimm.2024.11.004","DOIUrl":"10.1016/j.mucimm.2024.11.004","url":null,"abstract":"<div><div>The fungal community of the skin microbiome is dominated by a single genus, <em>Malassezia</em>. Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity. The mechanisms driving Th17 responses to <em>Malassezia</em> remain, however, unclear. Here, we show that the C-type lectin receptors Mincle, Dectin-1, and Dectin-2 recognize conserved patterns in the cell wall of <em>Malassezia</em> and induce dendritic cell activation <em>in vitro</em>, while only Dectin-2 is required for Th17 activation during experimental skin colonization <em>in vivo.</em> In contrast, Toll-like receptor recognition was redundant in this context. Instead, inflammatory IL-1 family cytokines signaling via MyD88 were also implicated in Th17 activation in a T cell-intrinsic manner. Taken together, we characterized the pathways contributing to protective immunity against the most abundant member of the skin mycobiome. This knowledge contributes to the understanding of barrier immunity and its regulation by commensals and is relevant considering how aberrant immune responses are associated with severe skin pathologies.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 205-219"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695758","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}