Mucosal Immunology最新文献

{"title":"Gut microbiota regulates intestinal goblet cell response and mucin production by influencing the TLR2-SPDEF axis in an enteric parasitic infection.","authors":"Yeganeh Yousefi, Zarin Haider, Jensine A Grondin, Huaqing Wang, Sabah Haq, Suhrid Banskota, Tyler Seto, Michael Surette, Waliul I Khan","doi":"10.1016/j.mucimm.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.03.007","url":null,"abstract":"<p><p>Alterations in goblet cell biology constitute one of the most effective host responses against enteric parasites. In the gastrointestinal (GI) tract, millions of bacteria influence these goblet cell responses by binding to pattern recognition receptors such as toll-like receptors (TLRs). Studies suggest that the gut microbiota also interacts bidirectionally with enteric parasites, including Trichuris muris. Here, we study the roles of T. muris-altered microbiota and the TLR2-SPDEF axis in parasitic host defense. In acute T. muris infection, we observed altered gut microbiota composition, which, when transferred to germ-free mice, resulted in increased goblet cell numbers, Th2 cytokines and Muc2 expression, as well as increased Tlr2. Further, antibiotic (ABX)-treated TLR2^-/- mice, despite having received the same T. muris-altered microbiota, displayed diminished Th2 response, Muc2 expression, and, intriguingly, diminished SPDEF expression compared to wildtype counterparts. When infected with T. muris, SPDEF^-/- mice exhibited a reduced Th2 response and altered microbial composition compared to SPDEF^+/+, particularly on day 14 post-infection, and this microbiota was sufficient to alter host goblet cell response when transferred to ABX-treated mice. Taken together, our findings suggest the TLR2-SPDEF axis, via T. muris-induced microbial changes, is an important regulator of goblet cell function and host's parasitic defense.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753442","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":"Chronological maturation of the skin immune barrier is topographically different.","authors":"Anikó Kapitány, Lilla Soltész, Vivien Stercel, Lilla Szabó, Orsolya Somogyi, Eszter Anna Janka, Viktória Nagy, Szilárd Póliska, Krisztián Gáspár, Zoltán Hendrik, Dániel Törőcsik, Zsolt Dajnoki, Andrea Szegedi","doi":"10.1016/j.mucimm.2025.03.004","DOIUrl":"10.1016/j.mucimm.2025.03.004","url":null,"abstract":"<p><p>Adult skin varies across regions, with differences in chemical, physical, microbiota, and immune barriers. However, data on topographical immune differences in other age groups are limited. This study aimed to explore the chronological maturation of the immune barrier in various skin regions. A TaqMan low-density array and immunohistochemical and immunofluorescence detection of various immune cells and mediators in sebaceous gland-rich (SGR) and gland-poor (GP) healthy skin were performed in children, adolescents, and adults. The maturation of SGR skin showed a general upward trend in the mRNA levels of most Th17-related molecules with a significant increase in IL-1B from childhood to adulthood, but with only a slight elevation between childhood and adolescence. In addition, T cell, Treg, dendritic cell (DC) counts, as well as the levels of several Th17-related proteins (IL-17, IL-10, IL-23, CCL20, S100A8, sfTSLP, LCN2), increased significantly with age. In GP skin, AHR mRNA levels decreased, while Th17-related protein levels increased, although only moderately. When comparing the two regions, SGR and GP skin were similar in childhood, with differences emerging in adolescence and becoming significant in adulthood, particularly in the IL-17 pathway, mainly produced by Th17 cells. Our results show a similarly directed maturation process in GP and SGR regions, with more pronounced development of the SGR skin immune barrier (with more immune cell infiltration and cytokine production) during and after the adolescence. This is likely to be related to the significant changes in the chemical and microbiota barriers of the SGR skin during adolescence, and may explain the high incidence of inflammatory skin diseases on the SGR skin of adolescents, highlighting the need for targeted skin care in this region.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753440","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":"Single-cell sequencing reveals the same heterogeneity of neutrophils in heatstroke-induced lung and liver injury.","authors":"Fuquan Wang, Yan Zhang, Miaomiao Sun, Mengyu Li, Yu Wang, Dingyu Zhang, Shanglong Yao","doi":"10.1016/j.mucimm.2025.03.005","DOIUrl":"10.1016/j.mucimm.2025.03.005","url":null,"abstract":"<p><p>Heatstroke (HS) is typically considered a sepsis-like syndrome caused by hyperthermia, often accompanied by multiple organ dysfunctions (MODS). To explore the mechanisms of MODS, we established a mouse model of HS by exposing mice to a hyperthermic and high-humidity environment. Then, we utilized single-cell RNA sequencing (scRNA-seq) to depict the cellular landscape of HS mice lung tissue and liver tissue. We found that the enhancement of neutrophil infiltration mediated by the \"Cxcr2-Cxcl2″ receptor-ligand pair is a prominent feature of HS-induced lung injury. By effectively suppressing the recruitment of neutrophils in HS-induced lung injury, the application of Cxcr2 inhibitor held positive implications for improving HS-induced lung injury. In addition to the chemotactic effect of immune cells on neutrophils, we identified a subcluster of fibroblasts labeled as Col14a1+, which possessed notable chemotactic factor-secretion characteristics and likely exerted a role in the early stages of neutrophil infiltration. Furthermore, our study unveiled significant heterogeneity among neutrophils within the HS-induced lung injury. Particularly, Cd177 + neutrophils exhibited a dominant presence, characterized by heightened pro-inflammatory responses and oxidative stress. In heatstroke-induced liver injury, neutrophils exhibited similar heterogeneous characteristics. Cd177 + neutrophils exhibited an enhanced ability to produce neutrophil extracellular traps (NETs) while lowering the levels of NETs can significantly improve heatstroke-induced lung and liver injury. Additionally, our study identified Cebpe as a key transcriptional regulatory factor in Cd177 + neutrophil differentiation. Knockdown of the expression of Cebpe can suppress the Cd177 + neutrophil differentiation and decrease the expression levels of NETs. Our research indicated a common heterogeneity in neutrophils during MODS in HS. Cd177 + neutrophils contributed to organ damage in HS, and Cebpe may serve as a crucial intervention target in the treatment of HS.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753512","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":"Airway epithelial cells as drivers of severe asthma pathogenesis.","authors":"Del Dorscheid, Gail M Gauvreau, Steve N Georas, Pieter S Hiemstra, Gilda Varricchi, Bart N Lambrecht, Gianni Marone","doi":"10.1016/j.mucimm.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.03.003","url":null,"abstract":"<p><p>Our understanding of the airway epithelium's role in driving asthma pathogenesis has evolved over time. From being regarded primarily as a physical barrier that could be damaged via inflammation, the epithelium is now known to actively contribute to asthma development through interactions with the immune system. The airway epithelium contains multiple cell types with specialized functions spanning barrier action, mucociliary clearance, immune cell recruitment, and maintenance of tissue homeostasis. Environmental insults may cause direct or indirect injury to the epithelium leading to impaired barrier function, epithelial remodelling and increased release of inflammatory mediators. In severe asthma, the epithelial barrier repair process is inhibited and the response to insults is exaggerated, driving downstream inflammation. Genetic and epigenetic mechanisms also maintain dysregulation of the epithelial barrier, adding to disease chronicity. Here, we review the role of the airway epithelium in severe asthma and how targeting the epithelium can contribute to asthma treatment.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742558","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":"Intrapulmonary-administered myeloid derived suppressor cells rescue mice from Pseudomonas aeruginosa infection and promote a regulatory/repair phenotype.","authors":"Maëlys Born-Bony, Clémentine Cornu, Bérengère Villeret, Valérie Gratio, Romé Voulhoux, Jean-Michel Sallenave","doi":"10.1016/j.mucimm.2025.03.001","DOIUrl":"10.1016/j.mucimm.2025.03.001","url":null,"abstract":"<p><p>Pseudomonas aeruginosa (P.aeruginosa) is a pathogenic opportunistic bacterium, classified as a priority by the WHO for the research of new treatments. As this bacterium is harmful through the inflammation and tissue damage it causes, we investigated the role of Myeloid Derived Suppressor Cells (MDSC) in P.aeruginosa infections and their potential as a therapeutic tool. Using both 'classically' obtained MDSC (through mice bone-marrow differentiation), and a new procedure developed here (using the ER-Hoxb8 hematopoietic cell line), we observed that after administering intra-nasally a lethal dose of P.aeruginosa (PAO1), intra-pulmonary transfer of MDSC, in both prophylactic and therapeutic protocols, markedly improves survival of P.aeruginosa infected animals. Mechanistically, with a sub-lethal dose of P.aeruginosa, we observed that MDSC transfer modulated lung tissue injury, down-regulated inflammatory responses and elicited lung repair. We further showed that WT-PAO1 and MDSC (and their subtypes PMN-MDSC and M-MDSC) could interact directly in vitro and in vivo, and that both PMN- and M-MDSC gene expression (assessed through RNA sequencing) was modulated after in vitro P.aeruginosa infection, and that WT-PAO1 (but not ΔFlic-PAO1) infection led to inhibition of T cell proliferation and promoted epithelial cell wound healing. Furthermore, we showed that the transcription factor Nr4A1 was up-regulated in both PMN- and M-MDSC- infected cells and may be an important mediator in the process. Altogether, we highlight a potential beneficial role of MDSC in P.aeruginosa infection responses and suggest that the unique properties of these cells make them attractive potential new therapeutic tools for patients with acute or chronic inflammatory diseases.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663925","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":"Hematopoietic MyD88 orchestrates the control of gut colonization by segmented filamentous bacteria.","authors":"Marie Cherrier, Teck Hui Teo, Renan Oliveira Corrêa, Marion Picard, Aurélie Couesnon, Corinne Lebreton, Francesco Carbone, Cécile Masson, Pamela Schnupf, Nadine Cerf-Bensussan, Valérie Gaboriau-Routhiau","doi":"10.1016/j.mucimm.2025.03.002","DOIUrl":"10.1016/j.mucimm.2025.03.002","url":null,"abstract":"<p><p>Host-microbiota cooperation is critical for successful intestinal homeostasis. The commensal segmented filamentous bacteria (SFB) are crucial for orchestrating the post-natal maturation of the host gut immune system and establishing a healthy state of physiological inflammation, which largely depends on their intimate attachment to the ileal mucosa. However, the signaling pathways used by SFB to induce gut immune responses and how such responses ultimately control SFB colonization remain controversial. Using gnotobiotic approaches, we showed that SFB load is controlled by complex interactions involving the gut microbiota and the host immune system. Therefore, to clearly determine the role of host immune responses induced by SFB in directly controlling their growth, immunodeficient mice monocolonized with SFB were used. Here, we show that in the absence of a complex microbiota, the humoral immune response is dispensable to control SFB growth in the jejunum and ileum, shortly and later after colonization. In contrast, MyD88 signaling in myeloid cells is critical for licensing interleukin (IL)-22 production by type 3 innate lymphoid cells (ILC3) and CD4⁺ T cells, which ultimately limits SFB expansion. Thus, by revisiting the hierarchy of immune mechanisms that directly control SFB growth, our results emphasize the necessary and sufficient role of a hematopoietic MyD88/IL-22 axis.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639752","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":"Spatially separated epithelium-associated and lamina propria neutrophils present distinct functional identities in the inflamed colon mucosa.","authors":"Lenore K Yalom, Caroline J Herrnreiter, Triet M Bui, Joey Lockhart, Enzo B Piccolo, Xingsheng Ren, Cenfu Wei, Anastasiia Serdiukova, Edward B Thorp, Parambir S Dulai, Ronen Sumagin","doi":"10.1016/j.mucimm.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.02.008","url":null,"abstract":"<p><p>Inflammatory Bowel Disease (IBD) features en masse neutrophil (PMN) infiltration of the colon tissue, where PMNs occupy spatially distinct niches, including the lamina propria mucosa (LPNs) and the crypt epithelium (epithelium-associated neutrophils or EANs). Spatial PMN localization is currently used as a clinical disease scoring parameter, and EAN presence has been correlated with disease severity prognosis and reduced response to therapy. Surprisingly, although PMN heterogeneity and their clinical relevance in IBD is now well-recognized, localization-driven PMN specialization has not been investigated. We found that following initial PMN influx during the active disease phase, EANs were near-completely resolved in both UC remission patients and in murine colitis, whereas LPNs persisted throughout the resolution phase, implicating EANs as likely drivers of disease. Local profiling of transcriptional programs (by murine and human single-cell RNA sequencing, coupled with human spatial RNA transcriptomics) and functional phenotypes, including real-time intravital imaging of murine LPNs versus EANs in inflamed colon revealed LPNs and EANs to have distinct functional identities. LPN programs allowed for heightened motility and pathogen uptake, whereas EANs were overrepresented by hyperactivated/pro-apoptotic states with elevated ROS and inflammatory TNFα production. Thus, we demonstrate that colon LPNs and EANs have distinct functional identities, with EANs exhibiting activated states and apparent cytotoxicity, which may actively contribute to tissue damage. Our findings further identify EANs as potential therapeutic targets for improving mucosal healing and sustaining clinical remission in UC.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586255","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":"Female sex hormones and the oral contraceptive pill modulate asthma severity through GLUT-1.","authors":"Alexandra C Brown, Olivia R Carroll, Jemma R Mayall, Nazanin Zounemat-Kermani, Samantha L E Vinzenz, Henry M Gomez, Ed F Mills, Richard Y Kim, Chantal Donovan, Katherine J Baines, Evan J Williams, Bronwyn S Berthon, Katie Wynne, Hayley A Scott, James W Pinkerton, Yike Guo, Philip M Hansbro, Paul S Foster, Peter A B Wark, Sven-Erik Dahlen, Ian M Adcock, Lisa G Wood, Jay C Horvat","doi":"10.1016/j.mucimm.2025.02.006","DOIUrl":"10.1016/j.mucimm.2025.02.006","url":null,"abstract":"<p><p>Females are disproportionately affected by asthma. An increased understanding of how female sex hormones influence key pathophysiological processes that underpin asthma may identify new, more effective asthma therapies, particularly for females with severe, poorly controlled asthma. We assessed the effects of oral ethinylestradiol/levonorgestrel (representing OCP use) and depot-medroxyprogesterone acetate (DMPA) and estradiol injections on key features of experimental asthma, and determined their effects on glucose transporter-1 (GLUT-1). The effects of OCP use on clinical asthma outcomes, and the relationships between estrogen receptors and type 2 (T2), non-T2, and GLUT-1 responses, in clinical asthma were also determined. OCP and DMPA reduce T2 responses, disease features, and lung expression of GLUT-1, whereas estradiol increases lung expression of GLUT-1, and results in severe, corticosteroid-insensitive, neutrophil-enriched disease, in experimental asthma. OCP use is associated with reduced T2 cytokine and GLUT-1 responses in clinical asthma. GLUT-1 expression is increased in sputum of severe asthmatics, and positively correlates with estrogen receptor expression and both T2 and non-T2 inflammatory responses. Significantly, OCP or GLUT-1 inhibition protects against obesity-associated or estradiol-induced, severe, experimental asthma, respectively. Together, these data show how female sex hormones and the OCP likely modulate asthma severity by modifying GLUT-1 responses in the airways.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531659","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":"Increased ocular plasma cells induce damaging α-synuclein⁺ microglia in autoimmune uveitis.","authors":"Minghao Li, Meng Feng, Tingting Liu, Songqi Duan, Xuejing Man, Xiaomeng Yuan, Lijie Wang, Yu Sun, Xunbin Wei, Qiang Fu, Baofa Sun, Wei Lin","doi":"10.1016/j.mucimm.2025.02.007","DOIUrl":"10.1016/j.mucimm.2025.02.007","url":null,"abstract":"<p><p>Autoimmune uveitis (AIU) is an immune-inflammatory disease that can lead to blindness. However, incomplete understanding of the involved immune cell subsets and their contributions to retinal injury has hindered the development of effective AIU therapies. Using single-cell RNA sequencing and immunofluorescence, we identified α-synuclein⁺ microglia as the primary subset of damaged ocular cells in the eyes of the experimental autoimmune uveitis (EAU) mouse model. Ocular-infiltrating plasma cells (PCs) were shown to express multiple inflammatory factors, particularly TNF-α, which promoted the production of α-synuclein⁺ microglia. Studies of heterogeneous PC subtypes revealed that MUC1^- PCs represent the primary pathogenic subset, secreting multiple cytokines. Although MUC1⁺ PCs expressed TGF-β, they exhibited long-lived characteristics and secreted IgG and IgM, thereby prolonging disease progression. Finally, the small G protein Rab1A, also expressed in the PCs of Vogt-Koyanagi-Harada (VKH) patients, was found to mediate autophagy and NF-κB expression, influencing PCs survival and inflammatory responses. Silencing or knocking down Rab1A in PCs inhibited their survival. This study elucidates potential mechanisms underlying the neuroimmune inflammatory response and highlights the previously unrecognized role of infiltrating PCs in AIU, offering novel therapeutic targets for this disease.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523990","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":"Interleukin-10 production by innate lymphoid cells restricts intestinal inflammation in mice.","authors":"Jing Li, Justin Jacobse, Jennifer M Pilat, Harsimran Kaur, Weihong Gu, Seung Woo Kang, Mark Rusznak, Hsin-I Huang, Julio Barrera, Pauline A Oloo, Joseph T Roland, Caroline V Hawkins, Andrew P Pahnke, Marian Khalil, M Kay Washington, Keith T Wilson, Christopher S Williams, R Stokes Peebles, Liza Konnikova, Yash A Choksi, Gianna Elena Hammer, Ken S Lau, Jeremy A Goettel","doi":"10.1016/j.mucimm.2025.02.005","DOIUrl":"10.1016/j.mucimm.2025.02.005","url":null,"abstract":"<p><p>Interleukin-10 (IL-10) is an immunomodulatory cytokine critical for intestinal immune homeostasis. IL-10 is produced by various immune cells but IL-10 receptor signaling in intestinal CX₃CR1⁺ mononuclear phagocytes is necessary to prevent spontaneous colitis in mice. Here, we utilized fluorescent protein reporters and cell-specific targeting and found that Rorc-expressing innate lymphoid cells (ILCs) produce IL-10 in response to anti-CD40-mediated intestinal inflammation. Deletion of Il10 specifically in Rorc-expressing ILCs led to phenotypic changes in intestinal macrophages and exacerbated both innate and adaptive immune-mediated models of experimental colitis. The population of IL-10⁺ producing ILCs shared markers with both ILC2 and ILC3 with nearly all ILC3s being of the NCR⁺ subtype. Interestingly, Ccl26 was enriched in IL-10⁺ ILCs and was markedly reduced in IL-10-deficient ILC3s. Since CCL26 is a ligand for CX₃CR1, we employed RNA in situ hybridization and observed increased numbers of ILCs in close proximity to Cx3cr1-expressing cells under inflammatory conditions. Finally, we generated transgenic Rorc^tdTomato reporter mice that faithfully marked RORγt⁺ cells that could rescue disease pathology and aberrant macrophage phenotype following adoptive transfer into mice with selective Il10 deficiency in ILC3s. These results demonstrate that IL-10 production by a population of ILCs functions to promote immune homeostasis in the intestine possibly via direct effects on intestinal macrophages.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483613","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}