NK cells inhibit T-bet-deficient, autoreactive Th17 cells.

Wu W, Shi S, Ljunggren HG, Cava AL, Van Kaer L, Shi FD, Liu R
Scand J Immunol. 2012 76 (6): 559-66

PMID: 22928727 · PMCID: PMC3600979 · DOI:10.1111/j.1365-3083.2012.02773.x

The differentiation and maintenance of Th17 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 Th1 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 Rorc and STAT3 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 Th17 cells through NK cell-derived production of IFN-γ. These results identify NK cells as critical regulators in the development of autoreactive Th17 cells and Th17-mediated pathology.

© 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

MeSH Terms (18)

Animals Autoantigens Cell Communication Cell Differentiation Cells, Cultured Cytokines Cytotoxicity, Immunologic Gene Expression Regulation Immune Tolerance Killer Cells, Natural Mice Mice, Inbred C57BL Mice, Knockout Nuclear Receptor Subfamily 1, Group F, Member 3 STAT3 Transcription Factor T-Box Domain Proteins Th1 Cells Th17 Cells

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