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RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis.


ABSTRACT: Th17 cells play a critical role in autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Response gene to complement (RGC)-32 is a cell cycle regulator and a downstream target of TGF-? that mediates its profibrotic activity. In this study, we report that RGC-32 is preferentially upregulated during Th17 cell differentiation. RGC-32-/- mice have normal Th1, Th2, and regulatory T cell differentiation but show defective Th17 differentiation in vitro. The impaired Th17 differentiation is associated with defects in IFN regulatory factor 4, B cell-activating transcription factor, retinoic acid-related orphan receptor ?t, and SMAD2 activation. In vivo, RGC-32-/- mice display an attenuated experimental autoimmune encephalomyelitis phenotype accompanied by decreased CNS inflammation and reduced frequency of IL-17- and GM-CSF-producing CD4+ T cells. Collectively, our results identify RGC-32 as a novel regulator of Th17 cell differentiation in vitro and in vivo and suggest that RGC-32 is a potential therapeutic target in multiple sclerosis and other Th17-mediated autoimmune diseases.

SUBMITTER: Rus V 

PROVIDER: S-EPMC6197070 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis.

Rus Violeta V   Nguyen Vinh V   Tatomir Alexandru A   Lees Jason R JR   Mekala Armugam P AP   Boodhoo Dallas D   Tegla Cosmin A CA   Luzina Irina G IG   Antony Paul A PA   Cudrici Cornelia D CD   Badea Tudor C TC   Rus Horea G HG  

Journal of immunology (Baltimore, Md. : 1950) 20170329 10


Th17 cells play a critical role in autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Response gene to complement (RGC)-32 is a cell cycle regulator and a downstream target of TGF-β that mediates its profibrotic activity. In this study, we report that RGC-32 is preferentially upregulated during Th17 cell differentiation. RGC-32<sup>-/-</sup> mice have normal Th1, Th2, and regulatory T cell differentiation but show defective Th17 dif  ...[more]

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