Mucosal Immunology最新文献

{"title":"Mitochondrial damage-associated molecular patterns: New perspectives for mitochondria and inflammatory bowel diseases","authors":"Zhijie Wang ,&nbsp;Zixuan He ,&nbsp;Xin Chang ,&nbsp;Lu Xie ,&nbsp;Yihang Song ,&nbsp;Haicong Wu ,&nbsp;Hao Zhang ,&nbsp;Shuling Wang ,&nbsp;Xiaofeng Zhang ,&nbsp;Yu Bai","doi":"10.1016/j.mucimm.2025.01.013","DOIUrl":"10.1016/j.mucimm.2025.01.013","url":null,"abstract":"<div><div>Mitochondria are key regulators of inflammatory responses and mitochondrial dysfunction is closely linked to various inflammatory diseases. Increasing genetic and experimental evidence suggests that mitochondria play a critical role in inflammatory bowel disease (IBD). In the complex environment of the intestinal tract, intestinal epithelial cells (IECs) and their mitochondria possess unique phenotypic features, shaping each other and regulating intestinal homeostasis and inflammation through diverse mechanisms. Here, we focus on intestinal inflammation in IBD induced by mitochondrial damage-associated molecular patterns (mtDAMPs), which comprise mitochondrial components and metabolic products. The pathogenic mechanisms of mtDAMP signaling pathways mediated by two major mtDAMPs, mitochondrial DNA (mtDNA) and mitochondrial reactive oxygen species (mtROS), are discussed.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 290-298"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374453","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":"Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of Treg cells","authors":"Chenchen Wang ,&nbsp;Tingting Yu ,&nbsp;Yuexin Wang ,&nbsp;Mengtong Xu ,&nbsp;Jingjing Wang ,&nbsp;Yan Zhao ,&nbsp;Qiangyou Wan ,&nbsp;Lu Wang ,&nbsp;Jie Yang ,&nbsp;Jie Zhou ,&nbsp;Bin Li ,&nbsp;Ying Yu ,&nbsp;Yujun Shen","doi":"10.1016/j.mucimm.2024.12.014","DOIUrl":"10.1016/j.mucimm.2024.12.014","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (T_reg) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E₂ (PGE₂), a bioactive lipid compound derived from arachidonic acid, can modulate T cell functions in a receptor subtype-specific manner. However, whether PGE₂ regulates T_reg cell function and contributes to IBD pathogenesis remains unclear. Here, we found that the PGE₂ receptor subtype 2 (EP2) is highly expressed in T_reg cells. T_reg cell-specific deletion of EP2 resulted in increased T_reg cell numbers, and enhanced granzyme B(GzmB) expression and immunosuppressive capacity of T_reg cells in mice. Adoptive transfer of EP2-deficient T_reg cells attenuated naïve CD4⁺ T cell transfer-induced colitis in Rag1^−/− mice. Mice with EP2-deficient T_reg cells were protected from 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sodium sulfate (DSS)-induced colitis. Pharmacological blockage of EP2 with PF-04418948 markedly alleviated DSS-induced colitis in mice in a T_reg-dependent manner. Mechanistically, activation of EP2 suppressed T_reg cell function, at least in part, through reduction of GzmB expression via PKA-mediated inhibition of NF-κB signaling. Thus, we identified the PGE₂/EP2 axis as a key negative modulator of T_reg cell function, suggesting EP2 inhibition as a potential therapeutic strategy for IBD treatment.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 418-430"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922095","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":"Tissue-resident natural killer cells derived from conventional natural killer cells are regulated by progesterone in the uterus","authors":"Bruna K. Tatematsu,&nbsp;Dorothy K. Sojka","doi":"10.1016/j.mucimm.2024.12.009","DOIUrl":"10.1016/j.mucimm.2024.12.009","url":null,"abstract":"<div><div>The murine uterus contains three subsets of innate lymphoid cells (ILCs). Innate lymphoid cell type 1 (ILC1) and conventional natural killer (cNK) cells seed the uterus before puberty. Tissue-resident NK (trNK) cells emerge at puberty and vary in number during the estrous cycle. Here, we addressed the origin of uterine trNK cells and the influence of ovarian hormones on their local activation and differentiation <em>in vivo.</em> We used parabiosed mice in combination with intravascular fluorescent antibody labeling and flow cytometry to distinguish tissue-resident from circulating immune cells. Additionally, we used C57BL/6J ovariectomized (OVX) and non-OVX mice supplemented with ovarian hormones to assess their effects on uterine trNK cell function. Strikingly, mice OVX at three weeks of age and analyzed as adults lacked uterine trNK cells unless progesterone was administered. Our parabiosis studies confirmed that the progesterone-responsive trNK cells are derived from peripheral cNK cells. Moreover, medroxyprogesterone 17-acetate-induced expansion of cNK-derived trNK cells was abolished by a progesterone receptor antagonist. These data reveal a novel, uterine-specific differentiation pathway of trNK cells that is tightly regulated by progesterone.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 390-401"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872606","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":"TIFA renders intestinal epithelial cells responsive to microbial ADP-heptose and drives colonic inflammation in mice","authors":"Lena Erkert ,&nbsp;Barbara Ruder ,&nbsp;Melanie Kabisch ,&nbsp;Reyes Gamez Belmonte ,&nbsp;Jay V. Patankar ,&nbsp;Miguel Gonzalez Acera ,&nbsp;Lena Schödel ,&nbsp;Mircea T. Chiriac ,&nbsp;Roodline Cineus ,&nbsp;Stylianos Gnafakis ,&nbsp;Tamara Leupold ,&nbsp;Oana-Maria Thoma ,&nbsp;Iris Stolzer ,&nbsp;Astrid Taut ,&nbsp;Veronika Thonn ,&nbsp;Sebastian Zundler ,&nbsp;Claudia Günther ,&nbsp;Andreas Diefenbach ,&nbsp;Anja A. Kühl ,&nbsp;Ahmed N. Hegazy ,&nbsp;Sebastian Zundler","doi":"10.1016/j.mucimm.2025.01.003","DOIUrl":"10.1016/j.mucimm.2025.01.003","url":null,"abstract":"<div><div>Intestinal immune homeostasis relies on intestinal epithelial cells (IECs), which provide an efficient barrier, and warrant a state of tolerance between the microbiome and the mucosal immune system. Thus, proper epithelial microbial sensing and handling of microbes is key to preventing excessive immunity, such as seen in patients with inflammatory bowel disease (IBD). To date, the molecular underpinnings of these processes remain incompletely understood. This study identifies TIFA as a driver of intestinal inflammation and an epithelial signaling hub between the microbiome and mucosal immune cells. TIFA was constitutively expressed in crypt epithelial cells and was highly induced in the intestine of mice and IBD patients with intestinal inflammation. We further identified IL-22 signaling via STAT3 as key mechanism driving TIFA expression in IECs. At the molecular level, we demonstrate that TIFA expression is essential for IEC responsiveness to the bacterial metabolite ADP-heptose. Most importantly, ADP-heptose-induced TIFA signaling orchestrates an inflammatory cellular response in the epithelium, with NF-κB and inflammasome activation, and high levels of chemokine production. Finally, mice lacking TIFA were protected from intestinal inflammation when subjected to a model of experimental colitis. In conclusion, our study implicates that targeting TIFA may be a strategy for future IBD therapy.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 453-466"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023987","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":"CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis","authors":"Taylor M. Benson ,&nbsp;Gary E. Markey ,&nbsp;Juliet A. Hammer ,&nbsp;Luke Simerly ,&nbsp;Monika Dzieciatkowska ,&nbsp;Kimberly R. Jordan ,&nbsp;Kelley E. Capocelli ,&nbsp;Kathleen M. Scullion ,&nbsp;Louise Crowe ,&nbsp;Sinéad Ryan ,&nbsp;Jennifer O. Black ,&nbsp;Taylor Crue ,&nbsp;Rachel Andrews ,&nbsp;Cassandra Burger ,&nbsp;Eóin N. McNamee ,&nbsp;Glenn T. Furuta ,&nbsp;Calies Menard-Katcher ,&nbsp;Joanne C. Masterson","doi":"10.1016/j.mucimm.2024.09.006","DOIUrl":"10.1016/j.mucimm.2024.09.006","url":null,"abstract":"<div><div>Atopic diseases such as Eosinophilic Esophagitis (EoE) often progress into fibrosis (FS-EoE), compromising organ function with limited targeted treatment options. Mechanistic understanding of FS-EoE progression is confounded by the lack of preclinical models and the heavy focus of research on eosinophils themselves. We found that macrophage accumulation precedes esophageal fibrosis in FS-EoE patients. We developed a FS-EoE model via chronic administration of oxazalone allergen, in a transgenic mouse over-expressing esophageal epithelial hIL-5 (<em>L2-IL5^OXA</em>). These mice display striking histopathologic features congruent with that found in FS-EoE patients. Unbiased proteomic analysis, using a unique extracellular-matrix (ECM) focused technique, identified an inflammation-reactive provisional basal lamina membrane signature and this was validated in two independent EoE patient RNA-sequencing/proteomic cohorts, supporting model significance. A wound healing signature was also observed involving hemostasis-associated molecules previously unnoted in EoE. We further identified the ECM glycoprotein, Tenascin-C (TNC), and the stress-responsive keratin-16 (KRT16) as IL-4 and IL-13 responsive mediators, acting as biomarkers of FS-EoE. To mechanistically address how the immune infiltrate shapes FS-EoE progression, we phenotyped the major immune cell subsets that coalesce with fibrosis in both the <em>L2-IL5^OXA</em> mice and in FS-EoE patients. We found that macrophage are required for matrisome and cytoskeletal remodeling. Importantly, we show that macrophage accumulation precedes esophageal fibrosis and provide a novel therapeutic target in FS-EoE as their depletion with anti-CSF1 attenuated reactive matrisome and cytoskeletal changes. Thus, macrophage-based treatments and the exploration of TNC and KRT16 as biomarkers may provide novel therapeutic options for patients with fibrostenosis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 105-120"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350419","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":"TRIM29 controls enteric RNA virus-induced intestinal inflammation by targeting NLRP6 and NLRP9b signaling pathways","authors":"Junying Wang ,&nbsp;Ling Wang ,&nbsp;Wenting Lu ,&nbsp;Naser Farhataziz ,&nbsp;Anastasia Gonzalez ,&nbsp;Junji Xing ,&nbsp;Zhiqiang Zhang","doi":"10.1016/j.mucimm.2024.10.004","DOIUrl":"10.1016/j.mucimm.2024.10.004","url":null,"abstract":"<div><div>Infections by enteric virus and intestinal inflammation are recognized as a leading cause of deadly gastroenteritis, and NLRP6 and NLRP9b signaling control these infection and inflammation. However, the regulatory mechanisms of the NLRP6 and NLRP9b signaling in enteric viral infection remain unexplored. In this study, we found that the E3 ligase TRIM29 suppressed type III interferon (IFN-λ) and interleukin-18 (IL-18) production by intestinal epithelial cells (IECs) when exposed to polyinosinic:polycytidylic acid (poly I:C) and enteric RNA viruses. Knockout of TRIM29 in IECs was efficient to restrict intestinal inflammation triggered by the enteric RNA viruses, rotavirus in suckling mice, and the encephalomyocarditis virus (EMCV) in adults. This attenuation in inflammation was attributed to the increased production of IFN-λ and IL-18 in the IECs and more recruitment of intraepithelial protective Ly6A⁺CCR9⁺CD4⁺ T cells in small intestines from TRIM29-deficient mice. Mechanistically, TRIM29 promoted K48-linked ubiquitination, leading to the degradation of NLRP6 and NLRP9b, resulting in decreased IFN-λ and IL-18 secretion by IECs. Our findings reveal that enteric viruses utilize TRIM29 to inhibit IFN-λ and inflammasome activation in IECs, thereby facilitating viral-induced intestinal inflammation. This indicates that targeting TRIM29 could offer a promising therapeutic strategy for alleviating gut diseases.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 135-150"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470340","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":"Pro-inflammatory NK-like T cells are expanded in the blood and inflamed intestine in Crohn’s disease","authors":"Cristina M. Chiarolla ,&nbsp;Axel R. Schulz ,&nbsp;Michael Meir ,&nbsp;Sebastian Ferrara ,&nbsp;Yin Xiao ,&nbsp;Simone Reu-Hofer ,&nbsp;Addi J. Romero-Olmedo ,&nbsp;Valeria Falcone ,&nbsp;Katja Hoffmann ,&nbsp;Maike Büttner-Herold ,&nbsp;Martina Prelog ,&nbsp;Andreas Rosenwald ,&nbsp;Hartmut Hengel ,&nbsp;Michael Lohoff ,&nbsp;Hyun-Dong Chang ,&nbsp;Nicolas Schlegel ,&nbsp;Henrik E. Mei ,&nbsp;Friederike Berberich-Siebelt","doi":"10.1016/j.mucimm.2024.11.001","DOIUrl":"10.1016/j.mucimm.2024.11.001","url":null,"abstract":"<div><div>Altered intestinal immune homeostasis leads to chronic inflammation in Crohn’s disease (CD). To address disease- and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with CD and healthy donors’ PBMCs. Chronic intestinal inflammation enforced activation, exhaustion, and terminal differentiation of CD4⁺ and CD8⁺ T cells and a relative enrichment of CD4⁺ regulatory T (Treg) cells. Moreover, enigmatic rare Treg subsets appeared upon inflammation, e.g. CD4⁺FOXP3⁺HLA-DR⁺TIGIT^– and CD4⁺FOXP3⁺CD56⁺, expressing pro-inflammatory IFN-γ upon <em>in vitro</em> stimulation. Some conventional T (Tcon) cells acquired NK-like features. In CD patients’ blood, not well studied CD16⁺CCR6⁺CD127⁺ T cells appeared, being CD4⁺ or CD8⁺, a phenotype inducible on healthy T cells by CD blood plasma. Upon CD16-mediated antibody binding, they could attain effector function. These findings suggest an uncommon pro-inflammatory innate-like differentiation of Treg and Tcon cells with acquisition of non-specific cytotoxicity. Most likely, this is both cause and consequence of intestinal inflammation during CD.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 162-175"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623077","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":"IgA facilitates the persistence of the mucosal pathogen Helicobacter pylori","authors":"Mariela Artola-Borán ,&nbsp;Lydia Kirsche ,&nbsp;Angela Fallegger ,&nbsp;Peter Leary ,&nbsp;Mine Tanriover ,&nbsp;Tanja Goodwin ,&nbsp;Gavin Geiger ,&nbsp;Siegfried Hapfelmeier ,&nbsp;Shida Yousefi ,&nbsp;Hans-Uwe Simon ,&nbsp;Isabelle C. Arnold ,&nbsp;Anne Müller","doi":"10.1016/j.mucimm.2024.11.006","DOIUrl":"10.1016/j.mucimm.2024.11.006","url":null,"abstract":"<div><div>IgA antibodies have an important role in clearing mucosal pathogens. In this study, we have examined the contribution of IgA to the immune control of the gastrointestinal bacterial pathogens <em>Helicobacter pylori</em> and <em>Citrobacter rodentium</em>. Both bacteria trigger a strong local IgA response that results in bacterial IgA coating in mice and in gastritis patients. Class switching to IgA depends on Peyer’s patches, T-cells, eosinophils, and eosinophil-derived TGF-β in both models. In the case of <em>H. pylori</em>, IgA secretion and bacterial coating also depend on a functional bacterial type IV secretion system, which drives the generation of Th17 cells and the IL-17-dependent expression of the polymeric immunoglobulin receptor PIGR. IgA^−/− mice are hypercolonized with <em>C. rodentium</em> in all examined tissues, suffer from more severe weight loss and develop more colitis. In contrast, <em>H. pylori</em> is controlled more efficiently in IgA^−/− mice than their WT counterparts. The effects of IgA deficiency of the offspring can be compensated by maternal IgA delivered by WT foster mothers. We attribute the improved immune control observed in IgA^−/− mice to IgA-mediated protection from complement killing, as <em>H. pylori</em> colonization is restored to wild type levels in a composite strain lacking both IgA and the central complement component C3. IgA antibodies can thus have protective or detrimental activities depending on the infectious agent.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 232-247"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710604","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 kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction","authors":"Wan-Bing Dai ,&nbsp;Xiao Zhang ,&nbsp;Xu-Liang Jiang ,&nbsp;Yi-Zhe Zhang ,&nbsp;Ling-Ke Chen ,&nbsp;Wei-Tian Tian ,&nbsp;Xiao-Xin Zhou ,&nbsp;Xiao-Yu Sun ,&nbsp;Li-Li Huang ,&nbsp;Xi-Yao Gu ,&nbsp;Xue-Mei Chen ,&nbsp;Xiao-Dan Wu ,&nbsp;Jie Tian ,&nbsp;Wei-Feng Yu ,&nbsp;Lei Shen ,&nbsp;Dian-San Su","doi":"10.1016/j.mucimm.2024.09.002","DOIUrl":"10.1016/j.mucimm.2024.09.002","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut–brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1–KYN pathway in the intestine could be a promising therapeutic target for POCD.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 1","pages":"Pages 53-65"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183289","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":"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}