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

Research output: Contribution to journalArticle

79 Citations (Scopus)

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.
LanguageEnglish
Pages2620-2626
Number of pages7
JournalJournal of Immunology
Volume184
Issue number5
DOIs
Publication statusPublished - 1 Mar 2010

Fingerprint

Autoantibodies
Arthritis
Mast Cells
Cytokines
Cell Degranulation
Adaptive Immunity
Rheumatoid Arthritis
Joints
Mastocytosis
Glucose-6-Phosphate Isomerase
Immunologic Factors
Interleukin-33
Interleukin-1
Innate Immunity
Fibroblasts
Inflammation

Keywords

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

Cite this

Xu, D., Jiang, H-R., Li, Y., Pushparaj, P. N., Kurowska-Stolarska, M., Leung, B. P., ... Liew, F. Y. (2010). IL-33 exacerbates autoantibody-induced arthritis. Journal of Immunology , 184(5), 2620-2626. https://doi.org/10.4049/jimmunol.0902685
Xu, Damo ; Jiang, Hui-Rong ; Li, Yubin ; Pushparaj, Peter N ; Kurowska-Stolarska, Mariola ; Leung, Bernard P ; Mu, Rong ; Tay, Hwee Kee ; McKenzie, Andrew N J ; McInnes, Iain B ; Melendez, Alirio J ; Liew, Foo Y. / IL-33 exacerbates autoantibody-induced arthritis. In: Journal of Immunology . 2010 ; Vol. 184, No. 5. pp. 2620-2626.
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Xu, D, Jiang, H-R, Li, Y, Pushparaj, PN, Kurowska-Stolarska, M, Leung, BP, Mu, R, Tay, HK, McKenzie, ANJ, McInnes, IB, Melendez, AJ & Liew, FY 2010, 'IL-33 exacerbates autoantibody-induced arthritis' Journal of Immunology , vol. 184, no. 5, pp. 2620-2626. https://doi.org/10.4049/jimmunol.0902685

IL-33 exacerbates autoantibody-induced arthritis. / Xu, Damo; Jiang, Hui-Rong; Li, Yubin; Pushparaj, Peter N; Kurowska-Stolarska, Mariola; Leung, Bernard P; Mu, Rong; Tay, Hwee Kee; McKenzie, Andrew N J; McInnes, Iain B; Melendez, Alirio J; Liew, Foo Y.

In: Journal of Immunology , Vol. 184, No. 5, 01.03.2010, p. 2620-2626.

Research output: Contribution to journalArticle

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T1 - IL-33 exacerbates autoantibody-induced arthritis

AU - Xu, Damo

AU - Jiang, Hui-Rong

AU - Li, Yubin

AU - Pushparaj, Peter N

AU - Kurowska-Stolarska, Mariola

AU - Leung, Bernard P

AU - Mu, Rong

AU - Tay, Hwee Kee

AU - McKenzie, Andrew N J

AU - McInnes, Iain B

AU - Melendez, Alirio J

AU - Liew, Foo Y

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N2 - 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.

AB - 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.

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KW - arthritis

KW - autoantibodies

KW - cell degranulation

KW - cytokines

KW - enzyme-linked immunosorbent assay

KW - interleukins

KW - mast cells

KW - mice

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Xu D, Jiang H-R, Li Y, Pushparaj PN, Kurowska-Stolarska M, Leung BP et al. IL-33 exacerbates autoantibody-induced arthritis. Journal of Immunology . 2010 Mar 1;184(5):2620-2626. https://doi.org/10.4049/jimmunol.0902685