ES-62 protects against collagen-induced arthritis by resetting interleukin-22 towards resolution of inflammation in the joints

Miguel A Pineda, David T Rodgers, Lamyaa Al-Riyami, William Harnett, Margaret Harnett

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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 interleukin-17 (IL-17) responses. The Th17 associated cytokine IL-22 also appears to have a pathogenic role in autoimmune arthritis, particularly in promoting proinflammatory responses by synovial fibroblasts and osteoclastogenesis. The present study was undertaken to investigate
whether the protection against joint damage afforded by ES-62 also reflects suppression of IL-22.
Methods. The role(s) of IL-22 was assessed by investigating the effects of neutralizing anti–IL-22 antibodies
and recombinant IL-22 (rIL-22) on proinflammatory cytokine production, synovial fibroblast responses,and joint damage in mice with CIA, with versus without exposure to ES-62.
Results. Neutralization of IL-22 during the initiation phase abrogated CIA, while administration of rIL-22 enhanced synovial fibroblast responses and exacerbated joint pathology. In contrast, after disease
onset anti–IL-22 did not suppress progression, whereas administration of rIL-22 promoted resolution of inflammation. Consistent with these late antiinflammatory effects, the protection afforded by ES-62 was associated with elevated levels of IL-22 in the serum and joints that
reflected a desensitization of the synovial fibroblast responses. Moreover, neutralization of IL-22 during the late effector stage of disease prevented ES-62–mediated
desensitization of synovial fibroblast responses and protection against CIA.
Conclusion. IL-22 plays a dual role in CIA, being pathogenic during the initiation phase while 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 synovial fibroblast responses and consequent protection against bone damage in RA.
Original languageEnglish
Pages (from-to)1492–1503
Number of pages12
JournalArthritis and Rheumatism
Volume66
Issue number6
Early online date4 Feb 2014
DOIs
Publication statusPublished - Jun 2014

Keywords

  • ES-62
  • synovial fibroblasts
  • collagen-induced arthritis
  • inflammation
  • IL-22

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