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Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function

The production and function of cytokines are highly regulated. One mechanism is the balance between pro- and anti-inflammatory cytokines. As interleukin (IL)-17A and IL-25 share the IL-17RA receptor chain, we hypothesize that IL-25 acts as an IL-17A receptor antagonist and limits its pro-inflammator...

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Autores principales: Lavocat, Fabien, Ndongo-Thiam, Ndiémé, Miossec, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449741/
https://www.ncbi.nlm.nih.gov/pubmed/28620392
http://dx.doi.org/10.3389/fimmu.2017.00647
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author Lavocat, Fabien
Ndongo-Thiam, Ndiémé
Miossec, Pierre
author_facet Lavocat, Fabien
Ndongo-Thiam, Ndiémé
Miossec, Pierre
author_sort Lavocat, Fabien
collection PubMed
description The production and function of cytokines are highly regulated. One mechanism is the balance between pro- and anti-inflammatory cytokines. As interleukin (IL)-17A and IL-25 share the IL-17RA receptor chain, we hypothesize that IL-25 acts as an IL-17A receptor antagonist and limits its pro-inflammatory effects. The production and expression kinetics of IL-25 and its receptor chains IL-17RA and RB were analyzed in rheumatoid synoviocytes alone or in coculture with peripheral blood mononuclear cells (PBMCs). The effects of autocrine or exogenous IL-25 on synoviocytes were investigated in the presence or not of an anti-IL-25 antibody. To study the regulatory effects of IL-25, synoviocytes and/or PBMCs were exposed to IL-25 before being treated with IL-17A and tumor necrosis factor alpha (TNF-α) alone or combined. IL-25, IL-6, and bioactive IL-17A were quantified in rheumatoid arthritis (RA) patient plasma. Synoviocytes expressed and secreted IL-25, and expressed the two chains of its receptor IL-17RA and IL-17RB. IL-17RB expression was increased by TNF-α. IL-25 production occurred at a delayed time point (5 days) after stimulation with IL-17A and TNF-α. Synoviocytes pretreated with IL-25 were less responsive to IL-17A and TNF-α. PBMCs exposed to IL-25 showed a decreased production of pro-inflammatory mediators, including IL-17A with a 57% decrease; p = 0.002. IL-25 levels were elevated in the plasma of RA patients compared to healthy subjects (p = 0.03). However, these levels are not high enough to inhibit the function of circulating IL-17A. In conclusion, it was shown for the first time that synoviocytes produce IL-25, specifically at late time points and that IL-25 acts as a regulator of IL-17A-driven inflammation, as indicated by in vitro results and in vivo, in a long-term RA patient follow-up. These results may be important when considering IL-17A inhibition.
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spelling pubmed-54497412017-06-15 Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function Lavocat, Fabien Ndongo-Thiam, Ndiémé Miossec, Pierre Front Immunol Immunology The production and function of cytokines are highly regulated. One mechanism is the balance between pro- and anti-inflammatory cytokines. As interleukin (IL)-17A and IL-25 share the IL-17RA receptor chain, we hypothesize that IL-25 acts as an IL-17A receptor antagonist and limits its pro-inflammatory effects. The production and expression kinetics of IL-25 and its receptor chains IL-17RA and RB were analyzed in rheumatoid synoviocytes alone or in coculture with peripheral blood mononuclear cells (PBMCs). The effects of autocrine or exogenous IL-25 on synoviocytes were investigated in the presence or not of an anti-IL-25 antibody. To study the regulatory effects of IL-25, synoviocytes and/or PBMCs were exposed to IL-25 before being treated with IL-17A and tumor necrosis factor alpha (TNF-α) alone or combined. IL-25, IL-6, and bioactive IL-17A were quantified in rheumatoid arthritis (RA) patient plasma. Synoviocytes expressed and secreted IL-25, and expressed the two chains of its receptor IL-17RA and IL-17RB. IL-17RB expression was increased by TNF-α. IL-25 production occurred at a delayed time point (5 days) after stimulation with IL-17A and TNF-α. Synoviocytes pretreated with IL-25 were less responsive to IL-17A and TNF-α. PBMCs exposed to IL-25 showed a decreased production of pro-inflammatory mediators, including IL-17A with a 57% decrease; p = 0.002. IL-25 levels were elevated in the plasma of RA patients compared to healthy subjects (p = 0.03). However, these levels are not high enough to inhibit the function of circulating IL-17A. In conclusion, it was shown for the first time that synoviocytes produce IL-25, specifically at late time points and that IL-25 acts as a regulator of IL-17A-driven inflammation, as indicated by in vitro results and in vivo, in a long-term RA patient follow-up. These results may be important when considering IL-17A inhibition. Frontiers Media S.A. 2017-05-31 /pmc/articles/PMC5449741/ /pubmed/28620392 http://dx.doi.org/10.3389/fimmu.2017.00647 Text en Copyright © 2017 Lavocat, Ndongo-Thiam and Miossec. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lavocat, Fabien
Ndongo-Thiam, Ndiémé
Miossec, Pierre
Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function
title Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function
title_full Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function
title_fullStr Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function
title_full_unstemmed Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function
title_short Interleukin-25 Produced by Synoviocytes Has Anti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function
title_sort interleukin-25 produced by synoviocytes has anti-inflammatory effects by acting as a receptor antagonist for interleukin-17a function
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449741/
https://www.ncbi.nlm.nih.gov/pubmed/28620392
http://dx.doi.org/10.3389/fimmu.2017.00647
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