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ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints

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...

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Autores principales: Pineda, Miguel A., Rodgers, David T., Al‐Riyami, Lamyaa, Harnett, William, Harnett, Margaret M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737104/
https://www.ncbi.nlm.nih.gov/pubmed/24497523
http://dx.doi.org/10.1002/art.38392
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author Pineda, Miguel A.
Rodgers, David T.
Al‐Riyami, Lamyaa
Harnett, William
Harnett, Margaret M.
author_facet Pineda, Miguel A.
Rodgers, David T.
Al‐Riyami, Lamyaa
Harnett, William
Harnett, Margaret M.
author_sort Pineda, Miguel A.
collection PubMed
description 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 in the presence or absence of 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.
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spelling pubmed-47371042016-02-11 ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints Pineda, Miguel A. Rodgers, David T. Al‐Riyami, Lamyaa Harnett, William Harnett, Margaret M. Arthritis Rheumatol Experimental Arthritis 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 in the presence or absence of 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. John Wiley and Sons Inc. 2014-05-27 2014-06 /pmc/articles/PMC4737104/ /pubmed/24497523 http://dx.doi.org/10.1002/art.38392 Text en © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/3.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Experimental Arthritis
Pineda, Miguel A.
Rodgers, David T.
Al‐Riyami, Lamyaa
Harnett, William
Harnett, Margaret M.
ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
title ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
title_full ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
title_fullStr ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
title_full_unstemmed ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
title_short ES‐62 Protects Against Collagen‐Induced Arthritis by Resetting Interleukin‐22 Toward Resolution of Inflammation in the Joints
title_sort es‐62 protects against collagen‐induced arthritis by resetting interleukin‐22 toward resolution of inflammation in the joints
topic Experimental Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737104/
https://www.ncbi.nlm.nih.gov/pubmed/24497523
http://dx.doi.org/10.1002/art.38392
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