Pineda, M. A. , Rodgers, D. T., Al-Riyami, L., Harnett, W. and Harnett, M. M. (2014) ES-62 protects against collagen-induced arthritis by resetting IL-22 towards resolution of inflammation in the joints. Arthritis and Rheumatology, 66(6), pp. 1492-1503. (doi: 10.1002/art.38392) (PMID:24497523)
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Abstract
Objective: The parasitic worm-derived immunomodulator, ES-62 protects against disease in the mouse collagen-induced arthritis (CIA) model of Rheumatoid Arthritis (RA) by suppressing pathogenic IL-17 responses. The Th17-associated cytokine, IL-22 also appears to play a pathogenic role in autoimmune arthritis, particularly in promoting pro-inflammatory responses by synovial fibroblasts (SF) and osteoclastogenesis. We therefore investigated whether the protection from joint damage afforded by ES-62 also reflected suppression of IL-22.<p></p> Methods: The role(s) of IL-22 were assessed by investigating the effects of neutralising anti-IL-22 antibodies and rIL-22 on pro-inflammatory cytokine production, synovial fibroblast responses and joint damage in mice with CIA, exposed to ES-62 or not.<p></p> Results: Neutralisation of IL-22 during the initiation phase abrogated CIA whilst administration of rIL-22 enhanced synovial fibroblast responses and exacerbated joint pathology. By contrast, after disease onset, anti-IL-22 did not suppress progression; rather, administration of rIL-22 promoted resolution of inflammation. Consistent with these late anti-inflammatory effects, the protection afforded by ES-62 was associated with elevated levels of IL-22 in the serum and joints that reflected a desensitisation of the synovial fibroblast responses. Moreover, neutralisation of IL-22 during the late effector stage of disease prevented ES-62-mediated desensitisation of synovial fibroblast responses and protection against CIA.<p></p> Conclusion: IL-22 plays a dual role in CIA, being pathogenic during the initiation phase whilst acting to resolve inflammation and joint damage during established disease. Harnessing of the tissue repair properties of IL-22 by ES-62 highlights the potential for joint-targeted therapeutic modulation of SF responses and consequent protection against bone damage in RA. © 2014 American College of Rheumatology.<p></p>
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Harnett, Professor Margaret and Al-Riyami, Dr Lamyaa and Pineda, Dr Miguel |
| Authors: | Pineda, M. A., Rodgers, D. T., Al-Riyami, L., Harnett, W., and Harnett, M. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Arthritis and Rheumatology |
| Publisher: | Wiley |
| ISSN: | 2326-5191 |
| ISSN (Online): | 2326-5205 |
| Copyright Holders: | Copyright © 2014 The Authors |
| First Published: | First published in Arthritis and Rheumatism 66(6):1492–1503 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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