Opposite functions of STAT3 and Smad3 in regulating Tiam1 expression in Th17 cells.

We recently showed that Tiam1 expression is induced in pro-inflammatory T helper 17 (Th17) cells differentiated with interleukin (IL)-6 and TGF-β1, and together with Rac1 promote Th17 cell development and autoimmunity in a mouse model of multiple sclerosis. Here we found that STAT3 and Smad3, downstream transcription factors of IL-6 and TGF-β1, respectively, play opposing roles in regulating Tiam1 transcription in CD4 T-cells. While IL-6-STAT3 signaling promotes Tiam1 expression, TGF-β1-Smad3 induces the opposite outcome.

Prediction and Validation of Transcription Factors Binding Sites in the Il9 Locus.

Over the past decade, multiple effector T cell subsets have been identified with varying differentiation conditions in the milieu as well as a broad diversity of cytokine expression. Interleukin-9 (IL-9) secreting T helper 9 (Th9) cells are the newest member of this family. T helper cell differentiation including Th9 cells appears to be an epigenetic phenomenon requiring the coordination of a large variety of transcription factors to reshape the chromatin landscape and generate various T helper phenotypes.

Tiam1/Rac1 complex controls Il17a transcription and autoimmunity.

RORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE.

Rheumatoid arthritis-associated RBPJ polymorphism alters memory CD4+ T cells.

Notch signaling has recently emerged as an important regulator of immune responses in autoimmune diseases. The recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional repressor, but converts into a transcriptional activator upon activation of the canonical Notch pathway. Genome-wide association studies of rheumatoid arthritis (RA) identified a susceptibility locus, rs874040(CC), which implicated the RBPJ gene.