IL-33 Exacerbates Autoantibody-Induced Arthritis

被引：103

作者：

Xu, Damo ^{[1
]}

Jiang, Hui-Rong ^{[1
]}

Li, Yubin ^{[1
]}

Pushparaj, Peter N. ^{[1
]}

Kurowska-Stolarska, Mariola ^{[1
]}

Leung, Bernard P. ^{[3
]}

Mu, Rong ^{[1
]}

Tay, Hwee Kee ^{[1
]}

McKenzie, Andrew N. J. ^{[2
]}

McInnes, Iain B. ^{[1
]}

Melendez, Alirio J. ^{[1
]}

Liew, Foo Y. ^{[1
]}

机构：

[1] Univ Glasgow, Glasgow Biomed Res Ctr, Fac Med, Div Immunol Infect & Inflammat, Glasgow G12 8TA, Lanark, Scotland

[2] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 05期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

RECEPTOR ACCESSORY PROTEIN; COLLAGEN-INDUCED ARTHRITIS; ANTIBODY-INDUCED ARTHRITIS; IL-1-LIKE CYTOKINE IL-33; HUMAN MAST-CELLS; RHEUMATOID-ARTHRITIS; IN-VIVO; MEDIATED ARTHRITIS; SERUM TRANSFER; ST2; COMPRISE;

D O I：

10.4049/jimmunol.0902685

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Rheumatoid arthritis pathogenesis comprises dysregulation in both innate and adaptive immunity. There is therefore intense interest in the factors that integrate these immunologic pathways in rheumatoid arthritis. In this paper, we report that IL-33, a novel member of the IL-1 family, can exacerbate anti-glucose-6-phosphate isomerase autoantibody-induced arthritis (AIA). Mice lacking ST2 (ST2(-/-)), the IL-33 receptor alpha-chain, developed attenuated AIA and reduced expression of articular proinflammatory cytokines. Conversely, treatment of wild-type mice with rIL-33 significantly exacerbated AIA and markedly enhanced proinflammatory cytokine production. However, IL-33 failed to increase the severity of the disease in mast cell-deficient or ST2(-/-) mice. Furthermore, mast cells from wild-type, but not ST2(-/-), mice restored the ability of ST2(-/-) recipients to mount an IL-33-mediated exacerbation of AIA. IL-33 also enhanced autoantibody-mediated mast cell degranulation in vitro and in synovial tissue in vivo. Together these results demonstrate that IL-33 can enhance autoantibody-mediated articular inflammation via promoting mast cell degranulation and proinflammatory cytokine production. Because IL-33 is derived predominantly from synovial fibroblasts, this finding provides a novel mechanism whereby a host tissue-derived cytokine can regulate effector adaptive immune response via enhancing innate cellular activation in inflammatory arthritis. The Journal of Immunology, 2010, 184: 2620-2626.

引用

页码：2620 / 2626

页数：7

共 47 条

[1] IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells [J].