Enforced expression of roquin protein in T cells exacerbates the incidence and severity of experimental arthritis

Young Rae Ji, Hei Jung Kim, Dong Hoon Yu, Ki Beom Bae, Seo Jin Park, Jun Koo Yi, Nari Kim, Si Jun Park, Keon Bong Oh, Sung Soo Hwang, Sanggyu Lee, Sung Hyun Kim, Myoung Ok Kim, Jeong Woong Lee, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

To investigate the role of Roquin, a RING-type ubiquitin ligase family member, we used transgenic mice with enforced Roquin expression in T cells, with collagen-induced arthritis (CIA). Wild-type (WT) and Roquin transgenic (Tg) mice were immunized with bovine type II collagen (CII). Arthritis severity was evaluated by clinical score; histopathologic CIA severity; proinflammatory and anti-inflammatory cytokine levels; anti- CII antibody levels; and populations of Th1, Th2, germinal center B cells, and follicular helper T cells in CIA. T cell proliferation in vitro and cytokine levels were determined to assess the response to CII. Roquin Tg mice developed more severe CIA and joint destruction compared with WT mice. Production of TNF-α, IFN-γ, IL-6, and pathogenic anti-collagen CII-specific IgG and IgG2a antibodies was increased in Roquin Tg mice. In addition, in vitro T cell assays showed increased proliferation and proinflammatory cytokine production in response to CII as a result of enforced Roquin expression in T cells. Furthermore, the Th1/Th2 balance was altered by an increased Th1 and decreased Th2 population. These findings suggest that overexpression of Roquin exacerbates the development of CIA and that enforced expression of Roquin in T cells may promote autoimmune diseases such as CIA.

Original languageEnglish (US)
Pages (from-to)42269-42277
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number50
DOIs
StatePublished - Dec 7 2012

Bibliographical note

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Fingerprint Dive into the research topics of 'Enforced expression of roquin protein in T cells exacerbates the incidence and severity of experimental arthritis'. Together they form a unique fingerprint.

Cite this