AUTHOR=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. 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1072420

DOI=10.3389/fimmu.2022.1072420

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Spondylarthritis (SpA) development in HLA-B27/human β2-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 Th<sub>17</sub> 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<sup>+</sup> regulatory T cells and inhibits Th<sub>17</sub> cells.</p></sec><sec><title>Methods</title><p>Here, we first investigated whether <italic>in vitro</italic> addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4<sup>+</sup> T cells. Next, we performed preclinical assay using IL-27 to investigate whether <italic>in vivo</italic> treatment could prevent SpA development in B27-rats.</p></sec><sec><title>Results</title><p><italic>in vitro</italic> addition of IL-27 to cocultures of cDCs and CD4<sup>+</sup> 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<sup>+</sup> T cells from SpA patients. Interestingly, <italic>in vivo</italic> treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4<sup>+</sup> T cells.</p></sec><sec><title>Discussion</title><p>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.</p></sec>