IL-33 exacerbates autoantibody-induced arthritis

Damo Xu, Hui-Rong Jiang, Yubin Li, Peter N Pushparaj, Mariola Kurowska-Stolarska, Bernard P Leung, Rong Mu, Hwee Kee Tay, Andrew N J McKenzie, Iain B McInnes, Alirio J Melendez, Foo Y Liew

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91 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)2620-2626
Number of pages7
JournalJournal of Immunology
Issue number5
Publication statusPublished - 1 Mar 2010


  • animals
  • arthritis
  • autoantibodies
  • cell degranulation
  • cytokines
  • enzyme-linked immunosorbent assay
  • interleukins
  • mast cells
  • mice


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