biostudies-literatureDart RJCancer Research UKMedical Research CouncilThe Francis Crick InstituteNational Institute for Health Research (NIHR)Wellcome Trusteadh0301https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615126biostudies-literatureUnknown381(6663)Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103⁺γδ T cell restoration was associated with sustained inflammatory bowel disease remission. Moreover, CD103⁺Vγ4⁺cell dysregulation and loss were also displayed by humans with germline BTNL3/BTNL8 hypomorphism, which we identified as a risk factor Science (New York, N.Y.)Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.PMC7615126FC001093108745CC2012094491/Z/10/Z106292/Z/14/ZFC001003108745/Z/15/Z100156100156/Z/12/ZCL-2014-01-005CC1107106292Kannambath SAmar AEast PZlatareva ITheodoridis EDart RJHayday ACParkes MRecaldin TLamb CAMansfield JCIrving PMPrescott NJVantourout PfalseConserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103⁺γδ T cell restoration was associated with sustained inflammatory bowel disease remission. Moreover, CD103⁺Vγ4⁺cell dysregulation and loss were also displayed by humans with germline BTNL3/BTNL8 hypomorphism, which we identified as a risk factor 2023-01-01T00:00:00Z2023 Sep2026-05-29T00:23:08.988Z2024-11-07T04:12:46.415ZS-EPMC76151263770826810.1126/science.adh0301