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One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-na\u00efve polyJIA patients compared to pediatric controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Blood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4\u2009+\u2009T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann\u2013Whitney U and Wilcoxon matched-pairs signed rank tests.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Treatment-na\u00efve polyJIA patients had increased Th17 cells (CD3\u2009+\u2009CD4\u2009+\u2009interleukin(IL)-17\u2009+) compared to controls (0.15% v 0.44%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), but Tregs (CD3\u2009+\u2009CD4\u2009+\u2009CD25\u2009+\u2009FOXP3\u2009+) from patients did not differ from controls. Changes in STAT3 phosphorylation in CD4\u2009+\u2009T cells following ex vivo stimulation were not significantly different in patients compared to controls. We identified dual IL-17\u2009+\u2009and interferon (IFN)\u03b3\u2009+\u2009expressing CD4\u2009+\u2009T cells in patients, but not controls. Further, both Th17\/1\u00a0s (CCR6\u2009+\u2009CD161\u2009+\u2009IFN\u03b3\u2009+\u2009IL-17\u2009+) and ex-Th17s (CCR6\u2009+\u2009CD161\u2009+\u2009IFN\u03b3\u2009+\u2009IL-17<jats:sup>neg<\/jats:sup>) were increased in patients\u2019 post-treatment (Th17\/1: 0.3% v 0.07%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 and ex-Th17s: 2.3% v 1.4%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The patients with the highest IL-17 expressing cells post-treatment remained therapy-bound.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Patients with polyJIA have increased baseline Th17 cells, potentially reflecting higher tonic STAT3 activation in vivo. These quantifiable immune markers may identify patients that would benefit upfront from pathway-focused biologic therapies. Our data also suggest that inflammatory CD4\u2009+\u2009T cell subsets not detected in controls but increased in post-treatment samples should be further evaluated as a tool to stratify patients in remission on medication. Future work will explore these proposed diagnostic and prognostic biomarkers.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-024-00965-5","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T08:01:49Z","timestamp":1709366509000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Th17\/1 and ex-Th17 cells are detected in patients with polyarticular juvenile arthritis and increase following treatment"],"prefix":"10.1186","volume":"22","author":[{"given":"Stephanie","family":"Wood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Branch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Vasquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietta M.","family":"DeGuzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Carmela","family":"Sagcal-Gironella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saimun","family":"Singla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-133X","authenticated-orcid":false,"given":"Tiphanie P.","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"issue":"9783","key":"965_CR1","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1016\/S0140-6736(11)60244-4","volume":"377","author":"B Prakken","year":"2011","unstructured":"Prakken B, Albani S, Martini A. 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