{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:22:27Z","timestamp":1792002147035,"version":"4.4.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is a systemic autoimmune disease marked by multi-organ inflammation. Its pathogenesis involves profound T-cell dysfunction, autoreactive B-cell activation, impaired CD8<jats:sup>+<\/jats:sup> T-cell responses, myeloid cell abnormalities, and dysregulated cytokine secretion. Central to cytokine-driven immune activation is the Janus kinase\/signal transducer and activator of transcription (JAK\/STAT) signaling pathway. Baricitinib, a selective oral JAK1\/2 inhibitor approved for rheumatoid arthritis, has been extensively studied in SLE. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We aimed to investigate STAT3 phosphorylation in CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells and CD11b<jats:sup>+<\/jats:sup> myeloid cells from patients with SLE using single-cell flow cytometry of peripheral blood mononuclear cells (PBMCs) stimulated <jats:italic>ex vivo<\/jats:italic> with interleukin-6 (IL-6) or IL-15. We quantified pSTAT3 induction and assessed the inhibitory effect of baricitinib. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Despite long-term immunomodulators, significant STAT3 activation was observed in T cells and myeloid cells upon IL-6 or IL-15 stimulation in patients with SLE. Baricitinib effectively inhibited STAT3 phosphorylation in these cell types, though its inhibitory effect was notably weaker following IL-15 stimulation compared to IL-6. Notably, baricitinib did not affect the proportion of interferon-\u03b3 (IFN-\u03b3)- or IL-17-expressing cells. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings highlight the cell-type and cytokine-specific effects of baricitinib and demonstrate its capacity to dampen IL-6- and IL-15-mediated STAT3 activation in key immune cell subsets. Our results support a precision medicine approach to JAK inhibition in SLE and reinforce the potential of baricitinib in modulating key inflammatory pathways.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1675350","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T05:36:14Z","timestamp":1761024974000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The effect of baricitinib on pSTAT3 levels in IL-6- or IL-15-stimulated PBMCs isolated from patients with SLE"],"prefix":"10.3389","volume":"16","author":[{"given":"G\u00e1bor 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