NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells

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 modulate...

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Bibliographic Details
Published in:The Journal of experimental medicine 2020-08, Vol.217 (8)
Main Authors: Babic, Marina, Dimitropoulos, Christoforos, Hammer, Quirin, Stehle, Christina, Heinrich, Frederik, Sarsenbayeva, Assel, Eisele, Almut, Durek, Pawel, Mashreghi, Mir-Farzin, Lisnic, Berislav, Van Snick, Jacques, Löhning, Max, Fillatreau, Simon, Withers, David R, Gagliani, Nicola, Huber, Samuel, Flavell, Richard A, Polic, Bojan, Romagnani, Chiara
Format: Article
Language:English
Subjects:
Animals
Arthritis, Experimental - genetics
Arthritis, Experimental - immunology
Arthritis, Experimental - pathology
Autoimmunity
Cytokines - genetics
Cytokines - immunology
Encephalomyelitis, Autoimmune, Experimental - genetics
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - pathology
Inflammation - genetics
Inflammation - immunology
Inflammation - pathology
Innate Immunity and Inflammation
Medicin och hälsovetenskap
Mice
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily K - genetics
NK Cell Lectin-Like Receptor Subfamily K - immunology
T-Box Domain Proteins - genetics
T-Box Domain Proteins - immunology
Th1 Cells - immunology
Th1 Cells - pathology
Th17 Cells - immunology
Th17 Cells - pathology
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Summary: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.
ISSN:0022-1007
1540-9538
1540-9538
DOI:10.1084/jem.20190133