{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:44:27Z","timestamp":1790621067851,"version":"4.1.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      SLE is a chronic autoimmune disease characterized by immune system dysregulation, including aberrant activation of B and T lymphocytes and overproduction of proinflammatory cytokines such as IL-21. Through the STAT3 signaling pathway, this cytokine plays a key role in SLE-promoting autoantibody production and immune imbalance. It has been reported that miRNAs, such as miR-155 and miR-21, could be overexpressed in SLE and contribute to the STAT3 pathway dysregulation. We aimed to analyze the association between miR-155 and miR-21 and the expression of\n                      <jats:italic>SOCS1<\/jats:italic>\n                      ,\n                      <jats:italic>PTEN<\/jats:italic>\n                      ,\n                      <jats:italic>PIAS3<\/jats:italic>\n                      , and\n                      <jats:italic>IL21<\/jats:italic>\n                      in PBMC from SLE patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      PBMC isolation was performed by density gradient centrifugation using Histopaque-1077, culture overnight, and seeded at a concentration of 1x10\n                      <jats:sup>6<\/jats:sup>\n                      cells\/mL in 24-well flat-bottom cell culture plates for subsequent stimulation with 0.5 \u03bcg\/mL ionomycin and 2.5 \u03bcg\/mL PMA. The expression levels of miR-155, miR-21,\n                      <jats:italic>SOCS1, PTEN, PIAS3<\/jats:italic>\n                      , and\n                      <jats:italic>IL21<\/jats:italic>\n                      were measured using the RT-qPCR technique. Western blotting determined the expression of SOCS1, PTEN, PIAS3, IL-21, and p-STAT3 proteins. IL-17A levels in cell culture supernatant were determined using ELISA to assess cell stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results showed an increased expression of miR-155 and miR-21 in SLE patients compared to HC in both, stimulated and non-stimulated PBMC. The increased miR-155 and miR-21 expression were associated with a decreased gene expression of\n                      <jats:italic>SOCS1<\/jats:italic>\n                      and\n                      <jats:italic>PTEN<\/jats:italic>\n                      . The\n                      <jats:italic>IL21<\/jats:italic>\n                      expression was observed in stimulated PBMC with higher levels in SLE patients. These also showed lower expression of SOCS1, PTEN, and PIAS3, while levels of IL-21 were increased in total protein from PBMC, culture cell supernatants and plasma levels. Overall, p-STAT3 was increased in the PBMC of SLE patients. Finally, miR-21 inversely correlated with\n                      <jats:italic>PIAS3<\/jats:italic>\n                      and\n                      <jats:italic>PTEN<\/jats:italic>\n                      and miR-155 with SOCS1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings highlight the association between miR-155 and miR-21 with target genes SOCS1, PTEN, and PIAS3, that may contribute to the aberrant activation of the STAT3 pathway and the overproduction of IL-21 in SLE patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1664409","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:32:02Z","timestamp":1770013922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Aberrant STAT3 activation and 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Jalisco, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo C.","family":"Ortiz-Lazareno","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social","place":["Guadalajara, Jalisco, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Vega-Cornejo","sequence":"additional","affiliation":[{"name":"Hospital General de Occidente, Secretar\u00eda de Salud Jalisco","place":["Guadalajara, Jalisco, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Armendariz-Borunda","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular en Medicina y Terapia G\u00e9nica, Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Jalisco, Mexico"]},{"name":"Tecnologico de Monterrey, Escuela de 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