IL-33 exacerbates autoantibody-induced arthritis

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Xu, Damo and Jiang, Hui-Rong and Li, Yubin and Pushparaj, Peter N and Kurowska-Stolarska, Mariola and Leung, Bernard P and Mu, Rong and Tay, Hwee Kee and McKenzie, Andrew N J and McInnes, Iain B and Melendez, Alirio J and Liew, Foo Y (2010) IL-33 exacerbates autoantibody-induced arthritis. Journal of Immunology, 184 (5). pp. 2620-2626. (https://doi.org/10.4049/jimmunol.0902685)

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Abstract

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.

ORCID iDs

Xu, Damo, Jiang, Hui-Rong, Li, Yubin ORCID logoORCID: https://orcid.org/0000-0003-0939-9524, Pushparaj, Peter N, Kurowska-Stolarska, Mariola, Leung, Bernard P, Mu, Rong, Tay, Hwee Kee, McKenzie, Andrew N J, McInnes, Iain B, Melendez, Alirio J and Liew, Foo Y;
CORE (COnnecting REpositories)