Reduced TCRγδ signal strength engages phosphatidylinositol 3-kinase (PI3K) to drive thymic development of IL-17A-secreting γδ T cells

Reduced TCRγδ signal strength manifest by constrained Syk activity engages PI3K to maintain expression of key master regulators of the IL-17 program; RORγt and c-Maf, and drive thymic development of IL-17A-secreting γδ T cells (γδ17 cells). Notably, inhibition of PI3K not only abrogates γδ17 cell development, but also permits γδ progenitors to adopt a type-I interferon gene expression signature that identifies a novel CD8(+)Sca-1(+) γδ T cell subset. Total γδ T cells were sorted from foetal C57BL/6 thymic lobes cultured for 8 days in the presence of a pan-PI3K inhibitor (ZSTK474) or under control conditions.