1. RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis.
- Author
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Rus V, Nguyen V, Tatomir A, Lees JR, Mekala AP, Boodhoo D, Tegla CA, Luzina IG, Antony PA, Cudrici CD, Badea TC, and Rus HG
- Subjects
- Animals, Cell Differentiation drug effects, Central Nervous System immunology, Central Nervous System physiopathology, Granulocyte-Macrophage Colony-Stimulating Factor biosynthesis, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Nuclear Proteins deficiency, Nuclear Proteins pharmacology, Receptors, Retinoic Acid genetics, Receptors, Retinoic Acid metabolism, Th1 Cells immunology, Th17 Cells immunology, Th17 Cells pathology, Cell Differentiation immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Gene Expression Regulation, Nuclear Proteins genetics, Nuclear Proteins physiology, Th17 Cells physiology
- 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-β 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 γt, 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., (Copyright © 2017 by The American Association of Immunologists, Inc.)- Published
- 2017
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