Constrained TCR{gamma}{delta}-associated Syk activity engages PI3K to facilitate thymic development of IL-17A-secreting {gamma}{delta} T cells

Murine 17 cells, which are T cells that bear the T cell receptor (TCR) and secrete interleukin-17A (IL-17A), are generated in the thymus and are critical for various immune responses. Although strong TCR signals are required for the development of interferon- (IFN-)–secreting cells (IFN cells), the generation of 17 cells requires weaker TCR signaling. Here, we demonstrated that constrained activation of the kinase Syk downstream of TCR was required for the thymic development of 17 cells. Increasing or decreasing Syk activity by stimulating TCR or inhibiting Syk, respectively, substantially reduced 17 cell numbers. This delimited Syk activity optimally engaged the phosphoinositide 3-kinase (PI3K)–Akt signaling pathway, which maintained the expression of master regulators of the IL-17 program, RORt and c-Maf. Inhibition of PI3K not only abrogated 17 cell development but also augmented the development of a distinct, previously undescribed subset of T cells. These CD8+Ly6a+ T cells had a type-I IFN gene expression signature and expanded in response to stimulation with IFN-β. Collectively, these studies elucidate how weaker TCR signaling engages distinct signaling pathways to specify the 17 cell fate and identifies a role for type-I IFNs in T cell development.
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news