CD200R1 is required for the development of γδ 17 T cells

Abstract

{gamma}{delta} 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. {gamma}{delta} T cells develop in foetal thymi in temporally controlled waves where, unlike {beta} T cells, many {gamma}{delta} T cells adopt their effector fate, becoming either IFN{gamma} or IL-17A-producers ({gamma}{delta}17 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. {gamma}{delta}17 T cells are potent IL-17A producers in skin therefore, the effect of CD200R1 on IL-17A production by {gamma}{delta}17 T cells was investigated. CD200R1 was found to promote IL-17A production by {gamma}{delta} T cells by supporting the development of {gamma}{delta}17 T cells, enhancing IL-17-producing and ROR{gamma}t+ {gamma}{delta} T cell numbers in foetal thymic organ cultures. To fulfil this role, CD200R1 acts either directly on developing {gamma}{delta} T cells, or indirectly on thymic stromal cells. This identifies CD200R1 as a critical novel regulator of {gamma}{delta}17 T cell development in early life, a key process for ensuring immunity, particularly at barrier sites.