Estradiol Inhibits Th17 Cell Differentiation through Inhibition of RORγT Transcription by Recruiting the ERα/REA Complex to Estrogen Response Elements of the RORγT Promoter

The Th17-defining transcription factor RORγt promotes glomerulonephritis.

Although Th17 responses may contribute to the pathogenesis of glomerulonephritis, whether the key transcription factor in Th17 cell development, RORγt, also promotes glomerulonephritis is unknown. Here, we induced crescentic glomerulonephritis in wild-type and RORγt-deficient (RORγt(-/-)) mice. RORγt(-/-) mice were protected from disease, with reduced histologic and functional injury and decrea...

Estradiol Inhibits Th17 Cell Differentiation

Small Molecule Inhibitors Targeting the Th17 Cell Transcription Factor RORγt for the Treatment of Autoimmune Diseases

Naïve CD4+ T helper cells can differentiate into Th1, Th2, Th17, T regulatory, Th9 and Th22 cells. Th1 cells are characterized by their production of IFNγ but not IL-4 and IL-5 while Th2 cells are characterized by their expression of IL-4 and IL-5 but not IFNγ. T-bet and GATA3 are the master transcription factors for Th1 and Th2 cells, respectively [1]. Th1 cells mediate cellular immunity again...

IL-6-mediated Th17 differentiation through RORγt is essential for the initiation of experimental autoimmune myocarditis.

AIMS Interleukin (IL)-17-producing helper T (Th17) cells have been proposed to participate in the pathogenesis of chronic inflammation, such as autoimmune myocarditis. IL-6 gene ablation confers the resistance to experimental autoimmune myocarditis (EAM). In this study, we have addressed the pathological roles of IL-6 in the regulation of Th17 cells in EAM. METHODS AND RESULTS To induce EAM, ...

Fyn promotes Th17 differentiation by regulating the kinetics of RORγt and Foxp3 expression.

Th17 cells constitute a proinflammatory CD4(+) T cell subset that is important for microbial clearance, but also are implicated as propagators of various autoimmune pathologies. Evidence suggests that Th17 cells share common progenitors with immunosuppressive CD4(+) inducible regulatory T cells (T(REG)) and that the developmental pathways of these two subsets are reciprocally regulated. In this...