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Trim33 mediates the proinflammatory function of Th17 cells.

Shinya Tanaka1,2, Yu Jiang3, Gustavo J Martinez1

  • 1Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX.

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|June 23, 2018
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Summary

Tripartite motif-containing 33 (Trim33) regulates T helper 17 (Th17) cell differentiation and function. Trim33 promotes pro-inflammatory Th17 responses by increasing IL-17 and decreasing IL-10 production.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-β (TGF-β) signaling is crucial for T cell differentiation, including regulatory T (T reg) and T helper 17 (Th17) cells.
  • The precise molecular mechanisms governing reciprocal T reg and Th17 differentiation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of tripartite motif-containing 33 (Trim33) in regulating Th17 cell differentiation and function.
  • To elucidate the mechanism by which Trim33 modulates TGF-β signaling in T cells.

Main Methods:

  • In vitro differentiation assays for Th17 and T reg cells.
  • Analysis of Trim33's interaction with Smad proteins and its recruitment to gene loci.
  • Chromatin remodeling analysis at the Il17a and Il10 gene loci.
  • In vivo studies using Trim33-deficient T cells in an autoimmune disease model.

Main Results:

  • Trim33 deficiency in T cells ameliorated experimental autoimmune disease.
  • Trim33 was essential for Th17 cell induction in vitro, but not T reg cell induction.
  • Loss of Trim33 led to enhanced IL-10 production, contrasting with Smad4's role.
  • Trim33 was recruited to Il17a and Il10 gene loci, dependent on Smad2, and mediated chromatin remodeling.

Conclusions:

  • Trim33 is a key regulator of Th17 cell differentiation and function.
  • Trim33 promotes the pro-inflammatory phenotype of Th17 cells by inducing IL-17 and suppressing IL-10 expression.
  • Trim33 acts as a critical modulator of TGF-β signaling in T cell differentiation.