Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.

Autor: Dart RJ; Peter Gorer Department of Immunobiology, King's College London at Guy's Hospital Campus, London, UK.; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK.; Department of Gastroenterology, Guy's and St Thomas' Foundation Trust, London, UK., Zlatareva I; Peter Gorer Department of Immunobiology, King's College London at Guy's Hospital Campus, London, UK.; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK., Vantourout P; Peter Gorer Department of Immunobiology, King's College London at Guy's Hospital Campus, London, UK.; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK., Theodoridis E; Peter Gorer Department of Immunobiology, King's College London at Guy's Hospital Campus, London, UK.; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK., Amar A; Department of Medical and Molecular Genetics, King's College London, London, UK., Kannambath S; National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC) Genomics Centre, King's College London, London, UK., East P; Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK., Recaldin T; GammaDelta Therapeutics Ltd., London, UK., Mansfield JC; Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Gastroenterology, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK., Lamb CA; Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Gastroenterology, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK., Parkes M; Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK., Irving PM; Department of Gastroenterology, Guy's and St Thomas' Foundation Trust, London, UK., Prescott NJ; Department of Medical and Molecular Genetics, King's College London, London, UK., Hayday AC; Peter Gorer Department of Immunobiology, King's College London at Guy's Hospital Campus, London, UK.; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2023 Sep 15; Vol. 381 (6663), pp. eadh0301. Date of Electronic Publication: 2023 Sep 15.
DOI: 10.1126/science.adh0301
Abstrakt: 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 for penetrating Crohn's disease (CD). Thus, BTNL-dependent selection and/or maintenance of distinct tissue-intrinsic γδ T cells appears to be an evolutionarily conserved axis limiting the progression of a complex, multifactorial, tissue-damaging disease of increasing global incidence.
Databáze: MEDLINE
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