{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:49:23Z","timestamp":1782103763063,"version":"3.54.5"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"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>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by dysregulated innate and adaptive immunity. Soluble mediators like cytokines critically shape immune responses and sustain chronic inflammation. Interleukin-10 (IL-10), typically anti-inflammatory, also exerts pro-inflammatory effects in SLE, for example by promoting B cell differentiation and autoantibody production. Despite growing interest in IL-10 as a biomarker or therapeutic target, its dual roles have been reported inconsistently, likely reflecting differences in disease context, clinical presentation, disease activity, and the local microenvironment, an issue addressed in this work.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To further clarify its role in lupus, we investigated its function in a toll-like receptor 7 (TLR7) agonist-induced murine model. By administering an antagonistic anti-IL-10 receptor (anti-IL-10R) antibody, we investigated its broad\n                      <jats:italic>in vivo<\/jats:italic>\n                      effects on the progression of lupus-like features and associated immune changes. We then examined the signaling pathways underlying observed immune alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL-10 showed both pro- and anti-inflammatory effects on immune cells; however, overall, it modestly limited disease progression, indicating that, under the given conditions, its regulatory, anti-inflammatory effects may slightly outweigh its pro-inflammatory actions. The most pronounced effects were seen in the CD4 T-cell compartment, where IL-10R blockade increased IL-17, while reducing regulatory T cell (T\n                      <jats:sub>reg<\/jats:sub>\n                      ) frequencies, IL-10 and slightly also interferon gamma (IFN-\u03b3) expression. Mechanistically, IL-10 activated similar downstream pathways in T effector cells (CD4\n                      <jats:sup>+<\/jats:sup>\n                      FoxP3\n                      <jats:sup>-<\/jats:sup>\n                      T\n                      <jats:sub>eff<\/jats:sub>\n                      ) and CD4\n                      <jats:sup>+<\/jats:sup>\n                      FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      T\n                      <jats:sub>reg<\/jats:sub>\n                      , with signal transducer and activator of transcription 3 (STAT3) signaling being most prominent. We speculate that the heightened sensitivity of T\n                      <jats:sub>regs<\/jats:sub>\n                      to IL-10R blockade may stem from slightly elevated IL-10R expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these findings highlight dual role of IL-10 in lupus and suggest how a single cytokine may trigger opposing immune effects via shared signaling pathways. Further research is needed to clarify how a pro-inflammatory context directs IL-10 signaling toward stimulatory or suppressive outcomes, informing new therapeutic strategies for diseases such as SLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1783769","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:33:57Z","timestamp":1782102837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-10 at the crossroads of immunity in TLR7-induced lupus"],"prefix":"10.3389","volume":"17","author":[{"given":"Johanna Pauline","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Amend","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medical Center - 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University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen Qian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Riechert","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medical Center - 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