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The anti-inflammatory cytokine interleukin (IL)-10 and its receptors IL-10R\u03b1 and IL-10R\u03b2 have IBD-associated single nucleotide polymorphisms. In the intestine, IL-10 signaling is essential for maintaining an anti-inflammatory state of myeloid cells and inducing regulatory T cells, thereby preventing intestinal inflammation linked to IBD development. However, its impact on the physiology and pathophysiology of intestinal fibroblasts is poorly understood. Here, we show that Il10ra deficiency leads to increased expression of a subset of genes in colonic fibroblasts, most of which are associated with the Type I interferon (IFN) and Type II IFN signaling pathways. In addition, Pdgfra-cre; Il10raf\/f mice aged 16 weeks or older develop chronic spontaneous colitis and subsequent fibrosis accompanied by enhanced infiltration by myeloid cells and effector CD4+ T cells in the lamina propria of the colon. Moreover, Pdgfra-cre; Il10raf\/f mice at 12 weeks of age exhibit more severe clinical symptoms than those of Il10raf\/f mice during dextran sodium sulfate\u2013induced colitis that can be suppressed by the administration of anti-IFNAR1 antibody but not anti-IFNGR1 antibody. Therefore, inhibition of the Type I IFN pathway via IL-10R\u03b1 signaling in fibroblasts is one of the IL-10\u2013dependent mechanisms underlying the prevention of large intestinal pathology.<\/jats:p>","DOI":"10.1093\/intimm\/dxag022","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:44:42Z","timestamp":1778240682000},"page":"610-625","source":"Crossref","is-referenced-by-count":1,"title":["The interleukin-10\/interleukin-10R\u03b1 axis in fibroblasts limits large intestinal pathology by suppressing Type I interferon signaling"],"prefix":"10.1093","volume":"38","author":[{"given":"Takayoshi","family":"Ito","sequence":"first","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, The University of Osaka , Suita, Osaka 565-0871 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University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Fukada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Motooka","sequence":"additional","affiliation":[{"name":"WPI Immunology Frontier Research Center, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka , Suita 565-0871 ,","place":["Japan"]},{"name":"Genome Information Research Center, Research Institute for Microbial Diseases, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Department of Infection Metagenomics, Research Institute for Microbial Diseases, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5435-4144","authenticated-orcid":false,"given":"Takayuki","family":"Ogino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Nakamura","sequence":"additional","affiliation":[{"name":"WPI Immunology Frontier Research Center, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka , Suita 565-0871 ,","place":["Japan"]},{"name":"Genome Information Research Center, Research Institute for Microbial Diseases, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Department of Infection Metagenomics, Research Institute for Microbial Diseases, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4552-783X","authenticated-orcid":false,"given":"Daisuke","family":"Okuzaki","sequence":"additional","affiliation":[{"name":"Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka , Suita 565-0871 ,","place":["Japan"]},{"name":"Genome Information Research Center, Research Institute for Microbial Diseases, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Center for Infectious Disease Education and Research, The University of Osaka , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology 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