The Protein Tyrosine Kinase Tec Regulates a CD44highCD62L- Th17 Subset (original) (raw)

The generation of Th17 cells has to be tightly controlled during an immune response. In this study, we report an increase in a CD44 high CD62L 2 Th17 subset in mice deficient for the protein tyrosine kinase Tec. CD44 high CD62L 2 Tec 2/2 CD4 + T cells produced enhanced IL-17 upon activation, showed increased expression levels of IL-23R and RORgt, and IL-23-mediated expansion of Tec 2/2 CD4 + T cells led to an increased production of IL-17. Tec 2/2 mice immunized with heat-killed Streptococcus pneumoniae displayed increased IL-17 expression levels in the lung postinfection with S. pneumoniae, and this correlated with enhanced pneumococcal clearance and reduced lung inflammation compared with Tec +/+ mice. Moreover, naive Tec 2/2 OT-II CD4 + T cells produced higher levels of IL-17 when cultured with OVA peptide-loaded bone marrow-derived dendritic cells that have been previously activated with heat-killed S. pneumoniae. Taken together, our data indicated a critical role for Tec in T cell-intrinsic signaling pathways that regulate the in vivo generation of CD44 high CD62L 2 effector/memory Th17 populations.