RelA and RelB Transcription Factors in Distinct Thymocyte Populations Control Lymphotoxin-Dependent Interleukin-17 Production in γδ T Cells

Abstract

The NF-κB transcription factor regulates numerous immune responses but its contribution to interleukin-17 (IL-17) production by Tcells is largely unknown. Here, we report that IL-17, but not interferon-γ (IFN-γ), production by γδ Tcells required the NF-κB family members RelA and RelB as well as the lymphotoxin-β-receptor (LTβR). In contrast, LTβR-NF-κB signaling was not involved in the differentiation of conventional αβ Th17 cells. Impaired IL-17 production in RelA- or RelB-deficient Tcells resulted in a diminished innate immune response to Escherichia coli infection. RelA controlled the expression of LT ligands in accessory thymocytes whereas RelB, acting downstream of LTβR, was required for the expression of RORγt and RORα4 transcription factors and the differentiation of thymic precursors into γδT17 cells. Thus, RelA and RelB within different thymocyte subpopulations cooperate in the regulation of IL-17 production by γδ Tcells and contribute to the host's ability to fight bacterial infections.