Tripartite motif-containing 33 (Trim33) determines the pathogenic function of Th17 cells

We report that Tripartite motif-containing 33 (Trim33), a protein that was previously associated with TGF-beta signaling, determines the pathogenic function of Th17 cells. Trim33 deficiency in T cells resulted in resistance to an autoimmune disease model. Lack of Trim33 did not impact TGF-beta signaling in mediating Foxp3 gene expression but greatly reduced TGF-beta induction of IL-17 production during Th17 cell differentiation. Importantly, we found TGF-beta not only increased IL-17 but also suppressed IL-10 expression; absence of Trim33 or Smad2 but not Smad4 in T cells enhanced IL-10 expression. In a Smad2-dependent manner, Trim33 was recruited to Il17 and Il10 gene loci and was crucial in appropriate histone modification accompanying Th17 differentiation.

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Tanaka S, Jiang Y, Martinez GJ, Tanaka K, Yan X, Kurosaki T, Kaartinen V, Feng XH, Tian Q, Wang X, Dong C