{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:04:29Z","timestamp":1789985069855,"version":"4.0.1"},"reference-count":111,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The chemokine CXCL10 contributes to early autoimmune rheumatic disease (ARD) development. Preclinical ARD stages exhibit dendritic cells (DCs), CD4+ T cells, and monocytes (CD14+ cells) dysregulation and an overreactive immunoprofile. The peroxisome proliferator-activated receptor (PPAR)\u03b2\/\u03b4 acts as a \u201cmolecular brake\u201d, limiting autoimmune overresponse. This study aims to investigate CXCL10 in human monocyte-derived mDCs, CD4+ T cells, and monocytes exposed to PPAR\u03b2\/\u03b4 agonist carbaprostacylin (cPGI2) or PPAR\u03b3 agonist rosiglitazone (RGZ), to verify drug-class-related effects. Tumor necrosis factor (TNF)\u03b1, interferon (IFN)\u03b3, synergistic inducers of CXCL10, and interleukin (IL)-10 were investigated. mDCs, CD4+ T cells, and CD14+ monocytes isolated from healthy donors\u2019 blood were cultured, specifically activated to mimic an overreactive phenotype, and treated for 24\u201348 h with\/without [10 \u03bcM] cPGI2 or [5 \u03bcM] RGZ (near therapy doses, respectively). Luminex assays quantified cell supernatant analytes; Real-time q-PCR measured cytokine and PPAR\u03b2\/\u03b4 mRNA expression. cPGI2, not RGZ, significantly decreased CXCL10 in mDCs and CD4+ T cells, reduced TNF\u03b1 in mDCs, CD4+ T and monocytes, and diminished IFN\u03b3 in mDCs. IL-10 did not change. cPGI2-induced CXCL10 downregulation, with TNF\u03b1 and IFN\u03b3 decrease, might be relevant, given its early activity in ARD development. Scenarios on PPAR\u03b2\/\u03b4 agonist re-positioning aimed at modulating CXCL10 might open opportunities to support ARD management and targeted therapy development.<\/jats:p>","DOI":"10.3390\/biom16091325","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:29:29Z","timestamp":1789133369000},"page":"1325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CXCL10 Is Inhibited by PPAR\u03b2\/\u03b4-Selective Activation in Human Monocyte-Derived Dendritic Cells, T Lymphocytes and Monocytes In Vitro: Insights into Autoimmune Rheumatic Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Gabriele","family":"Farina","sequence":"first","affiliation":[{"name":"Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Mariangela","family":"Sottili","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5662-5554","authenticated-orcid":false,"given":"Giada","family":"La Spina","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Stefania","family":"Gelmini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Simona","family":"Truglia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Fabrizio","family":"Conti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-2097","authenticated-orcid":false,"given":"Francesca Romana","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3339-3114","authenticated-orcid":false,"given":"Clara","family":"Crescioli","sequence":"additional","affiliation":[{"name":"Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100129","DOI":"10.1016\/j.jtauto.2021.100129","article-title":"Autoimmune rheumatic diseases: One or many diseases?","volume":"4","author":"Moutsopoulos","year":"2021","journal-title":"J. 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