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

Reduced TCR?d signal strength manifest by constrained Syk activity engages PI3K to maintain expression of key master regulators of the IL-17 program; ROR?t and c-Maf, and drive thymic development of IL-17A-secreting ?d T cells (?d17 cells). Notably, inhibition of PI3K not only abrogates ?d17 cell development, but also permits ?d progenitors to adopt a type-I interferon gene expression signature that identifies a novel CD8(+)Sca-1(+) ?d T cell subset. Overall design: Total ?d 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.