title: NK cells inhibit T-bet-deficient, autoreactive Th17 cells.
abstract: 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.
authors.affiliation: Department of Neurology and Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Shi
authors.forename: H-G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: A L
authors.initials: AL
authors.lastname: Cava
authors.forename: L
authors.initials: L
authors.lastname: Van Kaer
authors.forename: F-D
authors.initials: FD
authors.lastname: Shi
authors.forename: R
authors.initials: R
authors.lastname: Liu
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D001324:Autoantigens; D016207:Cytokines; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; D050796:STAT3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor