AUTHOR=Hammitzsch Ariane , Ossadnik Andreas , Bachmann Quirin , Merwald-Fraenk Helga , Lorenz Georg , Witt Matthias , Wiesent Franziska , Mühlhofer Heinrich , Simone Davide , Bowness Paul , Heemann Uwe , Arbogast Martin , Moog Philipp , Schmaderer Christoph 

TITLE=Increased interleukin-26 in the peripheral joints of patients with axial spondyloarthritis and psoriatic arthritis, co-localizing with CD68-positive synoviocytes

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1355824

DOI=10.3389/fimmu.2024.1355824

ISSN=1664-3224

ABSTRACT=<sec><title>Objectives</title><p><italic>IL26</italic> levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. <italic>IL26</italic> can be produced by Th17 cells and locally within joints by tissue-resident cells. <italic>IL26</italic> induces osteoblast mineralization <italic>in vitro</italic>. As osteoproliferation and Th17 cells are important factors in the pathogenesis of axial spondyloarthritis (axSpA), we aimed to clarify the cellular sources of <italic>IL26</italic> in spondyloarthritis.</p></sec><sec><title>Methods</title><p>Serum, peripheral blood mononuclear cells (<italic>n</italic> = 15–35) and synovial tissue (<italic>n</italic> = 3–9) of adult patients with axSpA, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and healthy controls (HCs, <italic>n</italic> = 5) were evaluated by ELISA, flow cytometry including PrimeFlow assay, immunohistochemistry and immunofluorescence and quantitative PCR.</p></sec><sec><title>Results</title><p>Synovial tissue of axSpA patients shows significantly more <italic>IL26</italic>-positive cells than that of HCs (<italic>p</italic> &lt; 0.01), but numbers are also elevated in PsA and RA patients. Immunofluorescence shows co-localization of <italic>IL26</italic> with CD68, but not with CD3, SMA, CD163, cadherin-11, or CD90. <italic>IL26</italic> is elevated in the serum of RA and PsA (but not axSpA) patients compared with HCs (<italic>p</italic> &lt; 0.001 and <italic>p</italic> &lt; 0.01). However, peripheral blood CD4<sup>+</sup> T cells from axSpA and PsA patients show higher positivity for <italic>IL26</italic> in the PrimeFlow assay compared with HCs. CD4<sup>+</sup> memory T cells from axSpA patients produce more <italic>IL26</italic> under Th17-favoring conditions (IL-1β and IL-23) than cells from PsA and RA patients or HCs.</p></sec><sec><title>Conclusion</title><p><italic>IL26</italic> production is increased in the synovial tissue of SpA and can be localized to CD68<sup>+</sup> macrophage-like synoviocytes, whereas circulating <italic>IL26</italic><sup>+</sup> Th17 cells are only modestly enriched. Considering the osteoproliferative properties of <italic>IL26</italic>, this offers new therapeutic options independent of Th17 pathways.</p></sec>