{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:05Z","timestamp":1753891145981,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007471","name":"Applied Basic Research Foundation of Yunnan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007471","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Rheumatic mitral stenosis (RMS) is the most common manifestation of rheumatic heart disease, with high morbidity and mortality. Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine associated with many autoimmune diseases. However, the relation between IL-35 expression and RMS remains unknown. We aimed to study IL-35 expression in RMS and its association with disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IL-35 concentration was analyzed in blood samples from 40 patients, including 20 moderate, 20 severe RMS, and 20 healthy controls by ELISA. Mitral valve (MV) IL-35 expression was determined by western blot and immunohistochemistry in patients with RMS (22 and 29 cases, respectively) in comparison to control specimens with mitral valve prolapsed (5 cases, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL-35 levels were significantly elevated in the blood of the RMS patients compared to those from healthy subjects(p&amp;lt;0.05) and positively correlated with the severity of RMS (r=0.317, p&amp;lt;0.05). The expression of IL-35 and its subunits (p35 and EBI3) was also detected in MV tissues of patients with moderate or severe RMS. The expression of IL-35 and its subunits (p35 and EBI3) had a positive association with the severity of RMS in MV tissues (r=0.528, p&amp;lt;0.01; r=0.561, p&amp;lt;0.001; r=0.456, p&amp;lt;0.01). Co-localization of p35 and EBI3 was seen in MV tissues of RMS patients in a predominantly perivascular pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show for the first time an increase of IL-35 level in the blood and MV tissues of RMS patients, which is strongly correlated with the severity of RMS. These results suggest that IL-35 plays an important regulatory role in the progression of RMS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1537497","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T07:15:50Z","timestamp":1744096550000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High interleukin-35 expression is associated with the severity of rheumatic mitral 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