NK Cells Inhibit T‐bet‐deficient, Autoreactive Th17 Cells

Abstract

Abstract The differentiation and maintenance of T h17 cells require a unique cytokine milieu and activation of lineage‐specific transcription factors. This process appears to be antagonized by the transcription factor T ‐bet, which controls the differentiation of T h1 cells. Considering that T ‐bet‐deficient ( T ‐bet −/− ) mice are largely devoid of natural killer ( NK ) cells due to a defect in the terminal maturation of these cells, and because NK cells can influence the differentiation of T helper cells, we investigated whether the absence of NK cells in T‐bet‐deficient mice contributes to the augmentation of autoreactive Th17 cell responses. We show that the loss of T‐bet renders the transcription factors R orc and STAT 3 highly responsive to activation by stimuli provided by NK cells. Furthermore, reconstitution of T ‐bet −/− mice with wild‐type NK cells inhibited the development of autoreactive T h17 cells through NK cell‐derived production of IFN ‐γ. These results identify NK cells as critical regulators in the development of autoreactive T h17 cells and T h17‐mediated pathology.