CD200R1 promotes the development of murine γδ17 T cells.

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 fetal thymi in temporally controlled waves where, unlike αβ T cells, many γδ T cells adopt their effector fate, becoming either IFN-γ 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 fetal thymus, where it supports the development of γδ17 T cells, enhancing γδ17 T-cell and RORγt+ γδ T-cell numbers in fetal 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.