NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells
Babic M., Dimitropoulos C., Hammer Q., Stehle C., Heinrich F., Sarsenbayeva A., Eisele A., Durek P., Mashreghi M-F., Lisnic B., Van Snick J., Löhning M., Fillatreau S., Withers DR., Gagliani N., Huber S., Flavell RA., Polic B., Romagnani C.
NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. Despite its established role as a potent activator of the immune system, NKG2D-driven regulation of CD4+ T helper (Th) cell–mediated immunity remains unclear. In this study, we demonstrate that NKG2D modulates Th1 and proinflammatory T-bet+ Th17 cell effector functions in vitro and in vivo. In particular, NKG2D promotes higher production of proinflammatory cytokines by Th1 and T-bet+ Th17 cells and reinforces their transcription of type 1 signature genes, including Tbx21. Conditional deletion of NKG2D in T cells impairs the ability of antigen-specific CD4+ T cells to promote inflammation in vivo during antigen-induced arthritis and experimental autoimmune encephalomyelitis, indicating that NKG2D is an important target for the amelioration of Th1- and Th17-mediated chronic inflammatory diseases.