Mucosal Immunology最新文献

{"title":"Integrin β7 sustains ileal humoral immunity and microbial biogeography during chronic TNF-driven ileitis","authors":"Zining Shen,&nbsp;Matthew D.P. Lebsack,&nbsp;Joshua D. Boyer,&nbsp;Christopher Tyler,&nbsp;Amruth Chilukuri,&nbsp;Mark Holton,&nbsp;Paul Jedlicka,&nbsp;Guillaume Urtecho,&nbsp;Jesus Rivera-Nieves","doi":"10.1016/j.mucimm.2026.100378","DOIUrl":"10.1016/j.mucimm.2026.100378","url":null,"abstract":"<div><div>Integrin α4β7 directs lymphocyte trafficking to the intestinal lamina propria (LP) and is a major therapeutic target in inflammatory bowel disease (IBD). Although integrin (Itg) β7 has been extensively studied in T-cell recruitment, its role in protective mucosal humoral immunity during chronic ileitis remains unclear.</div><div>To investigate the role of itg β7 in intestinal immune compartmentalization, we crossed TNFΔARE mice, which develop Crohn's-like ileocolitis with Itg β7-deficient mice. Intestinal inflammation, lymphocyte trafficking, ileal LP immune cell composition, IgA responses, and microbial community structure were assessed using histopathology, competitive homing assays, flow cytometry, mass cytometry, ELISA, and 16S rRNA gene sequencing.</div><div>β7 deficiency exacerbated TNF-driven ileitis in an age-dependent manner. Competitive homing assays demonstrated early impaired recruitment of β7-deficient lymphocytes to the ileal LP. This defect resulted in a selective reduction of intestinal B cells and antibody secreting cells (ASC), whereas T-cell migration to ileum remained largely preserved, indicating differential reliance of lymphocyte subsets on β7-mediated trafficking. Mass cytometry analysis of ileal leukocytes showed enrichment of α4β7 expression on B cells and ASC, providing a mechanistic basis for their selective dependence on β7. Consistent with impaired mucosal humoral immunity, β7-deficient mice exhibited significantly reduced fecal and serum IgA levels, associated with altered microbial community structure and disruption of normal mucosal–luminal microbial biogeography, with partial overlap with microbial community changes observed in IgA-deficient mice.</div><div>These findings identify β7 integrin as a non-redundant regulator of ileal mucosal humoral immunity during chronic TNF-driven ileitis. Beyond its established role in T cell trafficking, β7 sustains B-cell recruitment, IgA production, and microbial organization in the inflamed ileum, thereby limiting ileitis severity, although additional β7-dependent immune compartments, including αEβ7-associated intraepithelial lymphocyte populations, may also contribute to disease regulation.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 5","pages":"Article 100378"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412481","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":"Early postnatal eosinophil expansion associates with gut microbial-metabolic features and type 2 immunity in preterm infants","authors":"Huiyu Chen,&nbsp;Yihuang Huang,&nbsp;Luyang Hong,&nbsp;Jinglin Chen,&nbsp;Ningxin Luo,&nbsp;Xinhui Guo,&nbsp;Junyan Han,&nbsp;Shujuan Li,&nbsp;Weiyin Yu,&nbsp;Weili Yan,&nbsp;Yufeng Zhou,&nbsp;Lan Zhang,&nbsp;Siyuan Jiang,&nbsp;Yun Cao","doi":"10.1016/j.mucimm.2026.100383","DOIUrl":"10.1016/j.mucimm.2026.100383","url":null,"abstract":"<div><h3>Background</h3><div>Early postnatal gut colonization, microbial metabolite production, and immune maturation proceed in parallel. Although disruption has been linked to later allergic disease, cellular immune patterns remain insufficiently defined. Very and extremely preterm infants frequently develop eosinophilia, providing a setting to relate eosinophil dynamics to exposures and gut microbial-metabolic features.</div></div><div><h3>Methods</h3><div>We analyzed 15,795 CBC measurements from 734 preterm infants, together with fecal 16S profiling, metabolomics, eosinophil follow-up, and mouse perturbation experiments. Antibiotic and feeding exposures, microbiota, and metabolites were evaluated by longitudinal and integrated analyses; mouse experiments examined antibiotic responses with or without sodium butyrate.</div></div><div><h3>Results</h3><div>Eosinophils showed a transient postnatal trajectory, with highest levels at 3–4 weeks. Higher eosinophil levels were associated with greater antibiotic exposure, delayed feeding tolerance, and higher eosinophil counts during the first year of follow-up. During the peak window, eosinophil levels were inversely associated with gut microbial diversity, <em>Clostridium</em> abundance, and fecal short-chain fatty acids, particularly butyrate. In neonatal mice, antibiotics coincided with higher splenic eosinophils and intestinal ILC2/type-2 signatures, whereas sodium butyrate yielded profiles closer to controls.</div></div><div><h3>Conclusion</h3><div>Early eosinophil expansion in these infants represents a time-restricted immune trajectory associated with NICU exposures and microbial-metabolic features. <em>Clostridium</em>-butyrate signatures are candidate correlates warranting mechanistic and outcome validation.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 5","pages":"Article 100383"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437311","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":"From the gut to the lung: microbiota-associated metabolites as regulators of respiratory immunometabolism","authors":"Jun-Yan Xiang,&nbsp;Clifford C. Taggart,&nbsp;Aoife M. Rodgers","doi":"10.1016/j.mucimm.2026.100364","DOIUrl":"10.1016/j.mucimm.2026.100364","url":null,"abstract":"<div><div>The development and progression of respiratory diseases are influenced by both the local pulmonary microenvironment and the intestinal ecosystem. Research on the gut-lung axis has shown that diverse small-molecule metabolites produced or modified by the gut microbiota can cross the intestinal barrier and enter the systemic circulation, where they may modulate immune-cell response thresholds, functional polarisation, and inflammatory dynamics in the distal lung. The local respiratory microbiota may also contribute to the pulmonary metabolic microenvironment, although its role in metabolite production and immune regulation remains less clearly defined. This review summarises the metabolic features of the gut and respiratory microbiota, focusing on the production, systemic distribution, and immunomodulatory mechanisms of microbiota-associated metabolites, including short-chain fatty acids, other short-chain carboxylic acids, and amino acid-derived metabolites, with attention to their effects on respiratory immune-cell populations. These mechanisms include metabolite-sensing G protein-coupled receptor signalling, histone deacetylase inhibition, and aryl hydrocarbon receptor-dependent mucosal immune programmes. At the disease level, current evidence suggests that these metabolites mainly influence viral infections, bacterial infections, and chronic inflammatory lung diseases by regulating immune-response intensity, persistence, and tissue tolerance, rather than directly mediating pathogen clearance. Finally, this review discusses the key challenges and future directions for moving from associative studies to causal validation and translational applications.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 5","pages":"Article 100364"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295237","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 immune system in postnatal lung development.","authors":"Olivia B Parks, Juraj Stipka, John F Alcorn, Taylor Eddens","doi":"10.1016/j.mucimm.2026.100410","DOIUrl":"https://doi.org/10.1016/j.mucimm.2026.100410","url":null,"abstract":"<p><p>The human lungs begin their development early in gestation. Both in utero and postnatally, the lungs undergo intricate morphological changes, the complex regulation of which has been extensively studied for decades. Even before the first breath, immune cells migrate into the lungs in a specific temporal, wave-like manner. Recent evidence suggests that both innate and adaptive immune cells actively participate in alveolarization. In this article, we provide an overview of how the immune system interfaces with the developing lungs. By examining the pathways utilized by the immune system in this context, we can enhance our understanding of their roles in specific developmental processes. Further, we review the effects of dysregulated lung immunity on lung development and the role of immunity in bronchopulmonary dysplasia.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100410"},"PeriodicalIF":5.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112335","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":"Alternative splicing of CD244 restrains natural killer cells at the maternal-fetal interface.","authors":"Johan Siewiera, Ghilas Ferrat, Reem Al-Daccak, Nabila Jabrane-Ferrat","doi":"10.1016/j.mucimm.2026.100408","DOIUrl":"10.1016/j.mucimm.2026.100408","url":null,"abstract":"<p><p>Decidual natural killer (dNK) cells are the predominant lymphocyte population at the maternal-fetal interface during early pregnancy, where they support placentation, vascular remodelling and immune tolerance. Despite their abundance, the mechanisms governing their proliferative state remain poorly understood. Here, we show that first-trimester dNK cells reside in a stable non-cycling state characterized by G0/G1 arrest, suppression of proliferation-associated transcriptional programmes and attenuated kinase signalling. Unlike peripheral blood NK (pNK) cells, dNK cells did not proliferate in response to IL-15 stimulation or exposure to human cytomegalovirus-infected autologous decidual stromal cells, indicating entry into cell-cycle is actively restrained within the decidual compartment. Mechanistically, dNK cells exhibited altered CD244 splice-variant usage together with markedly reduced expression of the adaptor protein SAP (SH2D1A), accompanied by broad attenuation of Src, MAPK, and mTOR signalling. Blockade of the CD244-CD48 axis promoted dNK-cell cycle entry and modulated ERK and p38 activation, identifying this signalling axis as a regulator of proliferative quiescence. Furthermore, decidua-associated cytokines remodelled CD244 splice-variant usage and receptor expression in pNK cells, demonstrating that soluble microenvironmental cues are sufficient to reprogramme NK-cell signalling. Together, these findings reveal a mechanism by which the decidual microenvironment restrains NK-cell proliferation, promoting immune homeostasis at the maternal-fetal interface.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100408"},"PeriodicalIF":5.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075452","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":"Dietary choline prevents colitis-driven carcinogenesis via SLC5A7-dependent Notch1 degradation and goblet cell reprogramming.","authors":"Yang Li, Yating Fan, Yuan Yin, Xiaoliang Feng, Dan Zhu, Lei Dai","doi":"10.1016/j.mucimm.2026.100407","DOIUrl":"10.1016/j.mucimm.2026.100407","url":null,"abstract":"<p><p>Chronic inflammation is a major driver of colorectal tumorigenesis, with patients suffering from inflammatory bowel disease (IBD) exhibiting a significantly elevated risk of developing colitis-associated cancer (CAC). Although epidemiological studies link dietary choline to reduced colorectal cancer (CRC) risk, its mechanism in inflammation-driven carcinogenesis remains unclear. Here, we demonstrate that the high-affinity choline transporter SLC5A7 mediates the protective effects of choline against intestinal inflammation and tumor development. Using intestinal epithelial-specific SLC5A7 knockout mice, we found that SLC5A7 deficiency exacerbated dextran sulfate sodium (DSS)-induced colitis and enhanced azoxymethane (AOM)/DSS-driven tumorigenesis. Single-cell RNA sequencing revealed that SLC5A7 loss led to marked goblet cell depletion, impaired mucosal barrier integrity, and increased bacterial invasion. Mechanistically, SLC5A7 directly bound to Notch1 and promoted its proteasomal degradation, thereby relieving Notch1-mediated suppression of goblet cell differentiation. Furthermore, choline supplementation upregulated SLC5A7 expression and inhibited Notch1 signaling in human colonic epithelial cells and intestinal organoids. Critically, all protective effects of dietary choline were abolished in SLC5A7-deficient mice. Our study defines a previously unrecognized pathway-from nutrient intake to epithelial defense-wherein choline activates SLC5A7 to degrade Notch1, promote goblet cell differentiation, and enhance barrier function, thereby suppressing colitis and associated carcinogenesis. These findings establish SLC5A7 as a key nutrient-sensitive regulator of intestinal homeostasis and provide a mechanistic basis for choline-based strategies to prevent IBD and CAC.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100407"},"PeriodicalIF":5.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149062908","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 EphA2 with a novel EFNA3-mimetic peptide enhances vaginal epithelial barrier function: Running title: EFNA3-MAP enhancing the vaginal epithelial barrier.","authors":"Rodolfo D Vicetti Miguel, Mohan Liu, Jeremy V Smedley, Thomas L Cherpes","doi":"10.1016/j.mucimm.2026.100406","DOIUrl":"10.1016/j.mucimm.2026.100406","url":null,"abstract":"<p><p>Barrier protection provided by vaginal stratified squamous epithelium (SSE) is supported by estrogen (E)-mediated stimulation of ephrin-Eph signaling that promote desmosome expression and function. Conversely, loss of E induced by use of the contraceptive depot-medroxyprogesterone acetate (DMPA) or menopause reduces desmosome expression and weakens this epithelial barrier. We previously reported treating mice with DMPA lowers expression of the desmosomal cadherin desmoglein-1 (DSG1) in vaginal SSE by dampening EFNA3-mediated signaling whereas these effects are partially reversed by intravaginal administration of recombinant EFNA3 (rEFNA3) protein. Herein we extended these results, developing an EFNA3-mimetic agonist peptide (EFNA3-MAP) that engages the EphA2 receptor in vitro. In vivo, EFNA3-MAP penetrated vaginal SSE more effectively than rEFNA3 and restored DSG1 levels and vaginal epithelial thickness in DMPA-treated mice. It also reduced susceptibility of these mice to genital infection with bacterial and viral pathogens. In separate studies, we showed that EFNA3-MAP bioactivity depended on G-H loop aromatic residues and EphA2 engagement and that topical EFNA3-MAP restored vaginal epithelial thickness and DSG1 expression in DMPA-treated rhesus macaques. Together, current studies establish EFNA3-EphA2 signaling as a key regulator of vaginal SSE health and offer strong rationale to explore if EFNA3-MAP similarly enhances cutaneous SSE barrier function.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100406"},"PeriodicalIF":5.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017549","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":"Loss of kallikrein 5 expression exacerbates allergic skin inflammation including impairing filaggrin processing, promoting Th2 differentiation and inducing dysbiosis.","authors":"Andrea M Klingler, Sybele Vidyant, Santoshi Pyakurel, Kenyatta C M F Viel, Angela Good, Yrina Rochman, Sierra S Beach, Kalen Rossey, Michael Brusilovsky, Julie M Caldwell, Marc E Rothenberg, Nurit P Azouz","doi":"10.1016/j.mucimm.2026.100404","DOIUrl":"10.1016/j.mucimm.2026.100404","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic allergic skin disease with T helper 2 (Th2) cell predominance and epithelial barrier impairment. The serine protease kallikrein (KLK) 5 has an essential role in regulating keratinocyte desquamation and skin renewal. Increased expression and activity of KLK5 is sufficient to induce skin inflammatory responses including AD. We examined the consequences of Klk5 deficiency following exposures to the type 2-provoking agent calcipotriol in mice. Loss of KLK5 exacerbates a spectrum of AD-like responses including increased accumulation of skin eosinophils and langerhans cells, over-expression of an array of cytokines in the skin and exacerbated scratching behavior. Klk5^-/- mice demonstrated microbiome dysbiosis with enriched actinobacteria and reduced firmicutes in the skin, alteration in skin metabolites involved in the acetyl-CoA pathway and decreased expression of mature filaggrin monomers. Cutaneous application of Cis-Urocanic acid (cUCA) attenuated inflammatory responses, highlighting barrier dysfunction as a primary mechanism. We reveal an unappreciated role for KLK5 in inhibiting type 2 responses, acting through its roles in filaggrin processing and modulation of the skin microbiome and metabolome. Though KLK5 overactivation is known to contribute to several inflammatory skin disorders, our findings demonstrate that complete loss of KLK5 is also pathogenic in AD-like responses in mice.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100404"},"PeriodicalIF":5.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002218","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":"Microbiota-derived tryptophan metabolites shape Th2 lymphocyte responses via the aryl hydrocarbon receptor and metabolic reprogramming.","authors":"Lu Yao, Tanya Guevara Avella, Abhijeet J Kulkarni, Marlinde Waardenburg, Maria Isabel Delgado-Dolset, Tomasz Wypych, Avril Walters, Kristoff Nieves, Hannah Devotta, Songhui Kim, Emer Shannon, Nonhlanhla Lunjani, Jens Walter, Milena Sokolowska, Liam O'Mahony","doi":"10.1016/j.mucimm.2026.100405","DOIUrl":"10.1016/j.mucimm.2026.100405","url":null,"abstract":"<p><p>Allergic diseases are linked with changes in gut microbiota composition and metabolism, but the direct mechanisms linking microbial metabolism to T helper 2 (Th2) lymphocyte differentiation are still poorly understood. Colonization of gnotobiotic animals with Bifidobacterium longum and Clostridium sporogenes resulted in high levels of tryptophan-derived indole-3-lactic acid (ILA), indole-3-acrylic acid (IA), and indole-3-propionic acid (IPA), which correlated with suppressed Th2 responses. Indoxyl-3-sulfate (I3S) and IA reduced interleukin (IL)-4, IL-5 and IL-13 secretion from human Th2 polarized lymphocytes in an aryl-hydrocarbon receptor (AHR)-dependent manner. IA and IPA induced broader metabolic rewiring by reducing Th2 cell mitochondrial oxidative phosphorylation and reactive oxygen species damage. Microbial tryptophan metabolism may modulate human Th2 cell polarization, differentiation and function thereby linking allergy development to microbial processes. In addition, we have identified novel links between mitochondrial metabolic programs and Th2 lymphocyte polarization that are impacted by the microbial Stickland pathway derived metabolites IA and IPA.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100405"},"PeriodicalIF":5.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002225","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":"Mucosal-associated invariant T cells respond to colonic microbiome alterations during acute HIV infection.","authors":"Sinmanus Vimonpatranon, Sydney K Mika, Alina P S Pang, Kawthar Machmach, Noemia S Lima, Sucheta Godbole, Chayada Sajjaweerawan, Elizabeth R Longtine, Amy R Henry, Farida Laboune, Ellie Metz, Nisakorn Ratnaratorn, Yuwadee Phuang-Ngern, Carlo Sacdalan, Julie A Ake, Barbara L Shacklett, Johan K Sandberg, Rungsun Rerknimitr, Nittaya Phanuphak, Sandhya Vasan, Daniel C Douek, Michael J Corley, Alexandra Schuetz, Dominic Paquin-Proulx","doi":"10.1016/j.mucimm.2026.100403","DOIUrl":"10.1016/j.mucimm.2026.100403","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells are an unconventional subset of T cells that respond to vitamin B2 metabolites from a range of bacteria and fungi. We have previously reported that peripheral MAIT cells are activated during acute HIV infection (AHI) in a manner associated with markers of microbial translocation. Here, we characterized peripheral and colonic MAIT cells from people with HIV (PWH) during AHI and after ART initiated during AHI or chronic HIV infection (CHI) and investigated their interplay with the colonic microbiome. During AHI, both peripheral and colonic MAIT cells were activated and showed evidence of proliferation. MAIT cell activation in blood and colon were unrelated to viral load and to each other, suggesting compartmentalized responses. Colonic CD4 MAIT cells were reduced and their reduction was associated with viral load, suggesting a direct viral effect. In vitro experiments confirmed that CD4 MAIT cells are susceptible to HIV-1 infection. Finally, changes in colonic microbiome composition were evident already during AHI and were associated with peripheral blood MAIT cell activation and effector maturation. Thus, these findings indicate that viral replication and colonic microbiome perturbation are associated with distinct, compartment-specific components of the MAIT cell response during AHI.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100403"},"PeriodicalIF":5.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930262","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}