CD200R1 promotes the development of murine γδ17 T cells

Linley, Holly and Jaigirdar, Shafqat and Buckingham, Lucy and Cox, Joshua and Priestley, Megan and Hains, Anna and Saunders, Amy (2026) CD200R1 promotes the development of murine γδ17 T cells. Journal of Leukocyte Biology. ISSN 1938-3673

Abstract

γδ T cells are enriched at barrier sites such as skin, gut and lung, where they protect against cancer and infections, and promote healing. They detect diverse ligands in T cell receptor-dependent or independent manners, producing large quantities of pro-inflammatory cytokines. γδ T cells develop in foetal thymi in temporally controlled waves where, unlike αβ T cells, many γδ T cells adopt their effector fate, becoming either IFNγ or IL-17A-producers (γδ17 T cells). CD200R1 suppresses myeloid cell activity but has also been shown to promote innate lymphoid cell IL-17A production, enhancing psoriasis-like skin inflammation. γδ17 T cells are potent IL-17A producers in skin therefore, the effect of CD200R1 on IL-17A production by γδ17 T cells was investigated using CD200R1KO mice. CD200R1 was revealed to promote IL-17A production by γδ T cells in skin and lymphoid organs. Although CD200R1 is not expressed by adult γδ T cells, it is expressed by immature developing γδ T cells in foetal thymus where it supports the development of γδ17 T cells, enhancing IL-17-producing and RORγt+ γδ T cell numbers in foetal thymic organ cultures. This identifies CD200R1 as an important novel regulator of γδ17 T cell development in early life, a key process for ensuring immunity, particularly at barrier sites.