We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Gene Associated With Retinoid-Interferon-Induced Mortality 19 Attenuates Murine Autoimmune Arthritis by Regulation of Th17 and Treg Cells.
- Authors
Moon, Young‐Mee; Lee, Jennifer; Lee, Seon‐Yeong; Her, Yang‐Mi; Ryu, Jun‐Geol; Kim, Eun‐Kyung; Son, Hea‐Jin; Kwok, Seung‐Ki; Ju, Ji Hyeon; Yang, Chul‐Woo; Park, Sung‐Hwan; Kim, Ho‐Youn; Cho, Mi‐La
- Abstract
Objective STAT-3 is a key transcriptional factor in the interleukin-6 (IL-6)-mediated differentiation of Th17 cells. Because Th17 is believed to be a central player in rheumatoid arthritis (RA), we sought to evaluate whether an endogenous inhibitor of the STAT3 gene, GRIM-19 (gene associated with retinoid-interferon-induced mortality 19), could attenuate the progression and severity of murine collagen-induced arthritis (CIA) through suppression of Th17 cells and, reciprocally, could increase expression of Treg cells. Methods Overexpression of GRIM-19 was produced either by intravenous/intramuscular administration of a GRIM-19 overexpression vector in DBA1/J mice or by development of GRIM-19-transgenic (Tg) mice on a C57BL/6 background. Clinical signs were scored for arthritis severity, and mouse splenocytes, serum, and joint tissue were obtained for immunostaining and histologic analyses. Results The numbers of CD4+IL-17+ cells and CD4+pSTAT3+ cells were decreased, while the numbers of CD4+CD25+Foxp3+ cells and CD4+pSTAT5+ cells were increased, in both GRIM-19 vector-transfected and GRIM-19-Tg mice. Administration of the GRIM-19 overexpression vector into mice with CIA markedly suppressed the clinical and histologic signs of arthritis in the affected joints. Similarly, when CIA was induced in GRIM-19-Tg mice, the arthritis phenotype was markedly attenuated and the expression of inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor α, and IL-17) in the arthritic joints was also significantly reduced. Moreover, bone marrow-derived monocyte/macrophages obtained from GRIM-19-Tg mice showed attenuated RANKL-induced osteoclastogenesis in vitro. Conclusion GRIM-19 improved the clinical and histologic features of CIA and also inhibited osteoclast formation. These findings suggest that GRIM-19 may be a novel treatment agent for RA.
- Subjects
SOUTH Korea; ARTHRITIS; T cells; ACADEMIC medical centers; ANALYSIS of variance; ANIMAL experimentation; ENZYME-linked immunosorbent assay; FLOW cytometry; IMMUNOBLOTTING; MICE; MORTALITY; POLYMERASE chain reaction; RESEARCH funding; STATISTICS; U-statistics; GENOMICS; DATA analysis; DATA analysis software; GENETICS; PHYSIOLOGY
- Publication
Arthritis & Rheumatology, 2014, Vol 66, Issue 3, p569
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.38267