IL-33 exacerbates autoantibody-induced arthritis

Xu, D. et al. (2010) IL-33 exacerbates autoantibody-induced arthritis. Journal of Immunology, 184(5), pp. 2620-2626. (doi:10.4049/jimmunol.0902685) (PMID:20139274)

Xu, D. et al. (2010) IL-33 exacerbates autoantibody-induced arthritis. Journal of Immunology, 184(5), pp. 2620-2626. (doi:10.4049/jimmunol.0902685) (PMID:20139274)

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Publisher's URL: http://dx.doi.org/10.4049/jimmunol.0902685

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. The Journal of Immunology, 2010, 184: 2620-2626

Item Type:Articles
Keywords:ANTIBODY-INDUCED ARTHRITIS CELLS COLLAGEN-INDUCED ARTHRITIS DISEASE EXPRESSION HUMAN MAST-CELLS IL-1-LIKE CYTOKINE IL-33 IN-VIVO inflammation MECHANISM MEDIATED ARTHRITIS PATHWAY RECEPTOR ACCESSORY PROTEIN RHEUMATOID-ARTHRITIS SERUM TRANSFER ST2 COMPRISE T-CELLS Treatment
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo and Tay, Dr Hwee Kee and Pushparaj, Dr Peter and Melendez Romero, Dr Alirio and Li, Mr Yubin and Kurowska-Stolarska, Dr Mariola and Jiang, Dr Hui-Rong
Authors: Xu, D., Jiang, H.-R., Li, Y., Pushparaj, P. N., Kurowska-Stolarska, M., Leung, B. P., Mu, R., Tay, H. K., McKenzie, A. N. J., McInnes, I. B., Melendez Romero, A. J., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:05 February 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198III -IMMUNOLOGY
514991IL-33: a novel cytokine that integrates innate and adaptive immune activation in inflammatory arthritisDamo XuArthritis Research UK (ARC)18912III -IMMUNOLOGY
241511Characterisation of genes differentially expressed on subsets of T lymphocytesFoo LiewMedical Research Council (MRC)G9818261III -IMMUNOLOGY
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794RI INFECTION IMMUNITY & INFLAMMATION