Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37708268.
- Also identified by DOI 10.1126/science.adh0301 and PMC identifier 7615126.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>+</sup>γδ T cell restoration was associated with sustained inflammatory bowel disease remission. Moreover, CD103<sup>+</sup>Vγ4<sup>+</sup>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.
Medical subject headings
- Butyrophilins
- Inflammatory Bowel Diseases
- Receptors, Antigen, T-Cell, gamma-delta
- T-Lymphocyte Subsets