NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells
Marina Babić, Christoforos Dimitropoulos, Quirin Hammer, Christina Stehle, Frederik Heinrich, Assel Sarsenbayeva, Almut Eisele, Pawel Durek, Mir‐Farzin Mashreghi, Berislav Lisnić, Jacques Van Snick, Max Löhning, Simon Fillatreau, David R. Withers, Nicola Gagliani, Samuel Huber, Richard A. Flavell, Bojan Polić, Chiara Romagnani
Abstract
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.