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Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses.

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Title: Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses.
Authors: Jouhault, Quentin, Cherqaoui, Bilade, Jobart-Malfait, Aude, Glatigny, Simon, Lauraine, Marc, Hulot, Audrey, Morelle, Guillaume, Hagege, Benjamin, Ermoza, Kétia, El Marjou, Ahmed, Izac, Brigitte, Saintpierre, Benjamin, Letourneur, Franck, Rémy, Séverine, Anegon, Ignacio, Boissier, Marie-Christophe, Chiocchia, Gilles, Breban, Maxime, Araujo, Luiza M.
Source: Frontiers in Immunology; 2/2/2023, Vol. 14, p1-14, 14p
Subject Terms: REGULATORY T cells, T helper cells, SPONDYLOARTHROPATHIES, T cells, CYTOKINES
Abstract: Introduction: Spondylarthritis (SpA) development in HLA-B27/human b2-microglobulin transgenic rat (B27-rat) is correlated with altered conventional dendritic cell (cDC) function that promotes an inflammatory pattern of CD4+ T cells, including a biased expansion of pro-inflammatory Th17 population and imbalance of regulatory T cells cytokine profile. Transcriptomic analysis revealed that cDCs from B27-rats under express IL-27, an anti-inflammatory cytokine which induces the differentiation of IL-10+ regulatory T cells and inhibits Th17 cells. Methods: Here, we first investigated whether in vitro addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4+ T cells. Next, we performed preclinical assay using IL-27 to investigate whether in vivo treatment could prevent SpA development in B27-rats. Results: in vitro addition of IL-27 to cocultures of cDCs and CD4+ T cell subsets from B27-rats reduced IL-17 and enhanced IL-10 production by T cells. Likewise, IL-27 inhibited the production of IL-17 by CD4+ T cells from SpA patients. Interestingly, in vivo treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4+ T cells. Discussion: Overall, our results reveal a potent inhibitory effect of IL-27 and highlight this cytokine as a promising new therapeutic target in SpA, especially for SpA patients non responders to currently approved biotherapies. [ABSTRACT FROM AUTHOR]
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses.
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  Data: <searchLink fieldCode="AR" term="%22Jouhault%2C+Quentin%22">Jouhault, Quentin</searchLink><br /><searchLink fieldCode="AR" term="%22Cherqaoui%2C+Bilade%22">Cherqaoui, Bilade</searchLink><br /><searchLink fieldCode="AR" term="%22Jobart-Malfait%2C+Aude%22">Jobart-Malfait, Aude</searchLink><br /><searchLink fieldCode="AR" term="%22Glatigny%2C+Simon%22">Glatigny, Simon</searchLink><br /><searchLink fieldCode="AR" term="%22Lauraine%2C+Marc%22">Lauraine, Marc</searchLink><br /><searchLink fieldCode="AR" term="%22Hulot%2C+Audrey%22">Hulot, Audrey</searchLink><br /><searchLink fieldCode="AR" term="%22Morelle%2C+Guillaume%22">Morelle, Guillaume</searchLink><br /><searchLink fieldCode="AR" term="%22Hagege%2C+Benjamin%22">Hagege, Benjamin</searchLink><br /><searchLink fieldCode="AR" term="%22Ermoza%2C+Kétia%22">Ermoza, Kétia</searchLink><br /><searchLink fieldCode="AR" term="%22El+Marjou%2C+Ahmed%22">El Marjou, Ahmed</searchLink><br /><searchLink fieldCode="AR" term="%22Izac%2C+Brigitte%22">Izac, Brigitte</searchLink><br /><searchLink fieldCode="AR" term="%22Saintpierre%2C+Benjamin%22">Saintpierre, Benjamin</searchLink><br /><searchLink fieldCode="AR" term="%22Letourneur%2C+Franck%22">Letourneur, Franck</searchLink><br /><searchLink fieldCode="AR" term="%22Rémy%2C+Séverine%22">Rémy, Séverine</searchLink><br /><searchLink fieldCode="AR" term="%22Anegon%2C+Ignacio%22">Anegon, Ignacio</searchLink><br /><searchLink fieldCode="AR" term="%22Boissier%2C+Marie-Christophe%22">Boissier, Marie-Christophe</searchLink><br /><searchLink fieldCode="AR" term="%22Chiocchia%2C+Gilles%22">Chiocchia, Gilles</searchLink><br /><searchLink fieldCode="AR" term="%22Breban%2C+Maxime%22">Breban, Maxime</searchLink><br /><searchLink fieldCode="AR" term="%22Araujo%2C+Luiza+M%2E%22">Araujo, Luiza M.</searchLink>
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  Data: Frontiers in Immunology; 2/2/2023, Vol. 14, p1-14, 14p
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  Data: <searchLink fieldCode="DE" term="%22REGULATORY+T+cells%22">REGULATORY T cells</searchLink><br /><searchLink fieldCode="DE" term="%22T+helper+cells%22">T helper cells</searchLink><br /><searchLink fieldCode="DE" term="%22SPONDYLOARTHROPATHIES%22">SPONDYLOARTHROPATHIES</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink><br /><searchLink fieldCode="DE" term="%22CYTOKINES%22">CYTOKINES</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Introduction: Spondylarthritis (SpA) development in HLA-B27/human b2-microglobulin transgenic rat (B27-rat) is correlated with altered conventional dendritic cell (cDC) function that promotes an inflammatory pattern of CD4<superscript>+</superscript> T cells, including a biased expansion of pro-inflammatory Th17 population and imbalance of regulatory T cells cytokine profile. Transcriptomic analysis revealed that cDCs from B27-rats under express IL-27, an anti-inflammatory cytokine which induces the differentiation of IL-10+ regulatory T cells and inhibits Th17 cells. Methods: Here, we first investigated whether in vitro addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4<superscript>+</superscript> T cells. Next, we performed preclinical assay using IL-27 to investigate whether in vivo treatment could prevent SpA development in B27-rats. Results: in vitro addition of IL-27 to cocultures of cDCs and CD4<superscript>+</superscript> T cell subsets from B27-rats reduced IL-17 and enhanced IL-10 production by T cells. Likewise, IL-27 inhibited the production of IL-17 by CD4<superscript>+</superscript> T cells from SpA patients. Interestingly, in vivo treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4<superscript>+</superscript> T cells. Discussion: Overall, our results reveal a potent inhibitory effect of IL-27 and highlight this cytokine as a promising new therapeutic target in SpA, especially for SpA patients non responders to currently approved biotherapies. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3389/fimmu.2022.1072420
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