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

Autor:	Rus V; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201; vrus@umaryland.edu.; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201., Nguyen V; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201.; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201., Tatomir A; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201.; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201., Lees JR; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814., Mekala AP; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201.; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201., Boodhoo D; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201.; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201., Tegla CA; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201.; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201., Luzina IG; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201.; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201., Antony PA; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201., Cudrici CD; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892; and., Badea TC; Retinal Circuit Development and Genetics Unit, Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892., Rus HG; Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201.; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 May 15; Vol. 198 (10), pp. 3869-3877. Date of Electronic Publication: 2017 Mar 29.
DOI:	10.4049/jimmunol.1602158
Abstrakt:	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.)
Databáze:	MEDLINE
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