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

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Title
Enforced expression of roquin protein in T cells exacerbates the incidence and severity of experimental arthritis
Author(s)
Y R Ji; H J Kim; D H Yu; K B Bae; S J Park; J K Yi; N Kim; S J Park; K B Oh; S S Hwang; S Lee; S H Kim; M O Kim; Jeong Woong Lee; Z Y Ryoo
Bibliographic Citation
Journal of Biological Chemistry, vol. 287, no. 50, pp. 42269-42277
Publication Year
2012
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.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M112.374835
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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