{"id":41011,"date":"2025-08-16T06:48:14","date_gmt":"2025-08-16T04:48:14","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/16\/c10orf99-gpr15l-increases-susceptibility-to-colitis-and-colitis-induced-colorectal-cancer-via-gpr15-independent-mechanisms-while-mediating-gpr15-dependent-t-cell-migration-to-the-large-intestine-g\/"},"modified":"2025-08-16T06:48:14","modified_gmt":"2025-08-16T04:48:14","slug":"c10orf99-gpr15l-increases-susceptibility-to-colitis-and-colitis-induced-colorectal-cancer-via-gpr15-independent-mechanisms-while-mediating-gpr15-dependent-t-cell-migration-to-the-large-intestine-g","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/16\/c10orf99-gpr15l-increases-susceptibility-to-colitis-and-colitis-induced-colorectal-cancer-via-gpr15-independent-mechanisms-while-mediating-gpr15-dependent-t-cell-migration-to-the-large-intestine-g\/","title":{"rendered":"C10ORF99 (GPR15L) increases susceptibility to colitis and colitis-induced colorectal cancer via GPR15-independent mechanisms, while mediating GPR15-dependent T cell migration to the large intestine. Gerald J O&#8217;Connor"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2025 Aug 13:S1933-0219(25)00084-4. doi: 10.1016\/j.mucimm.2025.08.001. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>GPR15 is a homing receptor important for T cell migration to the large intestine, the primary site of inflammation in ulcerative colitis. Both GPR15 and its ligand, C10ORF99, represent potential therapeutic targets for the treatment of IBD; however, the roles of C10ORF99 in the large intestine are not fully elucidated. Here, we demonstrate that C10ORF99 is the non-redundant ligand of GPR15 mediating T cell migration to the large intestine. Furthermore, we demonstrate that C10ORF99 has GPR15-independent functions in the large intestine: C10ORF99 deficiency is protective in chemically induced colitis, and this appears to result from enhanced epithelial barrier regeneration. We found that C10ORF99 can inhibit intestinal epithelial proliferation in a cell-intrinsic manner. Additionally, due to this protection from colitis development in the absence of C10ORF99, C10ORF99 KO is also protected from colitis-associated colorectal cancer development. These data indicate that the deficiency of C10ORF99 can not only block pathogenic T cell migration to the large intestine, but can also promote epithelial barrier repair, potentially offering additional advantages for recovery from ulcerative colitis.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40816454\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20250816004811&amp;v=2.18.0.post9+e462414\">40816454<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2025.08.001\">10.1016\/j.mucimm.2025.08.001<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2025 Aug 13:S1933-0219(25)00084-4. doi: 10.1016\/j.mucimm.2025.08.001. Online ahead of print. ABSTRACT GPR15 is a homing receptor important for T cell migration to the large intestine, the primary site of inflammation in ulcerative colitis. Both GPR15 and its ligand, C10ORF99, represent potential therapeutic targets for the treatment of IBD; however, the roles of C10ORF99 in &#8230; <a title=\"C10ORF99 (GPR15L) increases susceptibility to colitis and colitis-induced colorectal cancer via GPR15-independent mechanisms, while mediating GPR15-dependent T cell migration to the large intestine. Gerald J O&#8217;Connor\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/16\/c10orf99-gpr15l-increases-susceptibility-to-colitis-and-colitis-induced-colorectal-cancer-via-gpr15-independent-mechanisms-while-mediating-gpr15-dependent-t-cell-migration-to-the-large-intestine-g\/\" aria-label=\"Read more about C10ORF99 (GPR15L) increases susceptibility to colitis and colitis-induced colorectal cancer via GPR15-independent mechanisms, while mediating GPR15-dependent T cell migration to the large intestine. Gerald J O&#8217;Connor\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[57,42],"tags":[],"class_list":["post-41011","post","type-post","status-publish","format-standard","hentry","category-mucosal-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41011","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=41011"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41011\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41011"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41011"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41011"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}