Developmentally regulated GTP-binding protein 2 ameliorates EAE by suppressing the development of TH17 cells

Myoung Seok Ko; Hyo Jeong Kim; Hong Kyung Kim; Nal Ae Yoon; Unn Hwa Lee; Sang Chul Lee; Dae Kyun Chung; Byung Ju Lee; Jae Hee Suh; Wha Ja Cho; Jeong Woo Park

doi:10.1016/j.clim.2013.12.004

Developmentally regulated GTP-binding protein 2 ameliorates EAE by suppressing the development of TH17 cells

Clin Immunol. 2014 Feb;150(2):225-35. doi: 10.1016/j.clim.2013.12.004. Epub 2013 Dec 17.

Authors

Affiliations

¹ Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea; Department of Medical Science, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
² Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
³ Personalized Medicine System R&D Center, Bio-Support Co., Ltd., Anyang, Kyeonggi-Do 431-810, South Korea.
⁴ School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin 449-701, South Korea.
⁵ Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, South Korea.
⁶ Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, South Korea.
⁷ Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea. Electronic address: jwpark@ulsan.ac.kr.

PMID: 24463315
DOI: 10.1016/j.clim.2013.12.004

Abstract

Developmentally regulated GTP-binding protein 2 (DRG2) represents a novel subclass of GTP-binding proteins. We here report that transgenic overexpression of DRG2 in mice ameliorates experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The protective effect of DRG2 in EAE was mediated by the inhibition of the development of T(H)17 cells. DRG2 enhanced the activity of PPARγ, which led to an inhibition of the nuclear factor kappa B (NF-κB) activity and IL-6 production in antigen presenting cells and an inhibition of the development of T(H)17 cells. Our results demonstrate that DRG2 is an essential modulator of EAE.

Keywords: DRG2; EAE; IL-6; NF-κB; PPARγ; T(H)17.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen-Presenting Cells / immunology
Antigen-Presenting Cells / metabolism
Cell Differentiation
Co-Repressor Proteins / metabolism
Cytokines / metabolism
Encephalomyelitis, Autoimmune, Experimental / genetics*
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / metabolism
GTP-Binding Proteins / genetics*
GTP-Binding Proteins / metabolism
Gene Expression
Genotype
Inflammation Mediators / metabolism
Interleukin-6 / genetics
Interleukin-6 / metabolism
Male
Mice
Mice, Transgenic
NF-kappa B / metabolism
PPAR gamma / metabolism
Promoter Regions, Genetic
Protein Binding
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
Th17 Cells / cytology
Th17 Cells / immunology*
Th17 Cells / metabolism

Substances

Co-Repressor Proteins
Cytokines
Inflammation Mediators
Interleukin-6
NF-kappa B
PPAR gamma
developmentally regulated GTP-binding protein
GTP-Binding Proteins