Enforced expression of roquin protein in T cells exacerbates the incidence and severity of experimental arthritis.
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.
School of Life Sciences and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Korea.
Young Rae
YR
Ji
Hei Jung
HJ
Kim
Dong Hoon
DH
Yu
Ki Beom
KB
Bae
Seo Jin
SJ
Park
Jun Koo
JK
Yi
Nari
N
Kim
Si Jun
SJ
Park
Keon Bong
KB
Oh
Sung Soo
SS
Hwang
Sanggyu
S
Lee
Sung-Hyun
SH
Kim
Myoung Ok
MO
Kim
Jeong Woong
JW
Lee
Zae Young
ZY
Ryoo
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases