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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.
LanguageEnglish
Pages1492–1503
Number of pages12
JournalArthritis and Rheumatism
Volume66
Issue number6
Early online date4 Feb 2014
DOIs
Publication statusPublished - Jun 2014

Fingerprint

Experimental Arthritis
Joints
Inflammation
Fibroblasts
interleukin-22
Rheumatoid Arthritis
Cytokines
Interleukin-17
Helminths
Immunologic Factors
Osteogenesis
Arthritis
Anti-Inflammatory Agents

Keywords

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

Cite this

Pineda, Miguel A ; Rodgers, David T ; Al-Riyami, Lamyaa ; Harnett, William ; Harnett, Margaret . / ES-62 protects against collagen-induced arthritis by resetting interleukin-22 towards resolution of inflammation in the joints. In: Arthritis and Rheumatism. 2014 ; Vol. 66, No. 6. pp. 1492–1503.
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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 investigatewhether 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 antibodiesand 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 diseaseonset 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 thatreflected a desensitization of the synovial fibroblast responses. Moreover, neutralization of IL-22 during the late effector stage of disease prevented ES-62–mediateddesensitization 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 toresolve inflammation and joint damage during establisheddisease. Harnessing of the tissue repair properties of IL-22 by ES-62 highlights the potential forjoint-targeted therapeutic modulation of synovial fibroblast responses and consequent protection against bone damage in RA.",
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ES-62 protects against collagen-induced arthritis by resetting interleukin-22 towards resolution of inflammation in the joints. / Pineda, Miguel A ; Rodgers, David T ; Al-Riyami, Lamyaa; Harnett, William; Harnett, Margaret .

In: Arthritis and Rheumatism, Vol. 66, No. 6, 06.2014, p. 1492–1503.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ES-62 protects against collagen-induced arthritis by resetting interleukin-22 towards resolution of inflammation in the joints

AU - Pineda, Miguel A

AU - Rodgers, David T

AU - Al-Riyami, Lamyaa

AU - Harnett, William

AU - Harnett, Margaret

PY - 2014/6

Y1 - 2014/6

N2 - 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 investigatewhether 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 antibodiesand 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 diseaseonset 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 thatreflected a desensitization of the synovial fibroblast responses. Moreover, neutralization of IL-22 during the late effector stage of disease prevented ES-62–mediateddesensitization 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 toresolve inflammation and joint damage during establisheddisease. Harnessing of the tissue repair properties of IL-22 by ES-62 highlights the potential forjoint-targeted therapeutic modulation of synovial fibroblast responses and consequent protection against bone damage in RA.

AB - 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 investigatewhether 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 antibodiesand 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 diseaseonset 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 thatreflected a desensitization of the synovial fibroblast responses. Moreover, neutralization of IL-22 during the late effector stage of disease prevented ES-62–mediateddesensitization 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 toresolve inflammation and joint damage during establisheddisease. Harnessing of the tissue repair properties of IL-22 by ES-62 highlights the potential forjoint-targeted therapeutic modulation of synovial fibroblast responses and consequent protection against bone damage in RA.

KW - ES-62

KW - synovial fibroblasts

KW - collagen-induced arthritis

KW - inflammation

KW - IL-22

UR - http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%292326-5205

U2 - 10.1002/art.38392

DO - 10.1002/art.38392

M3 - Article

VL - 66

SP - 1492

EP - 1503

JO - Arthritis and Rheumatism

T2 - Arthritis and Rheumatism

JF - Arthritis and Rheumatism

SN - 0004-3591

IS - 6

ER -