{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:16:55Z","timestamp":1789676215373,"version":"4.0.1"},"reference-count":146,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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:p>\n                    <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                    genital tract infection is linked to severe reproductive complications in women, including ectopic pregnancy, infertility, and adverse pregnancy outcomes. Mouse models of infection suggest that chlamydia\n                    <jats:italic>-<\/jats:italic>\n                    induced dysregulation of microRNAs (miRNAs) can drive harmful cytokine responses, pathogenic epithelial-mesenchymal transition (EMT), and fibrosis. To investigate these mechanisms in humans, we profiled miRNA and mRNA expression in endometrial biopsies from women with endometrial infection (Endo+) and compared them to profiles from women with cervix-only infection (Endo-) or no infection. Ingenuity Pathway Analysis (IPA) revealed that Endo+ tissues had upregulated genes associated with innate and adaptive immune response pathways, as well as EMT regulation, while downregulated genes were linked to cell cycle control. An integrative miRNA-mRNA analysis, which combined a review of published miRNA regulation in human infections and immune responses with IPA\u2019s miRNA target filter, identified differentially expressed miRNAs that modulate these pathways in the endometrium of Endo+ women. Functional annotation of these miRNAs showed a predominance of downregulated miRNAs that typically suppress EMT and regulatory T cell (Treg) differentiation, along with miRNAs that usually enhance Th17 responses. Comparisons with previously identified mRNA pathways in blood samples from women with endometrial\n                    <jats:italic>Chlamydia<\/jats:italic>\n                    infection indicated that alterations in TGF-\u03b2 signaling and EMT were specific to the endometrium. Overall, the miRNA-mRNA interactions inferred from Endo+ tissue suggest increased activity in TGF-\u03b2 pathways that promote enhanced EMT and Treg differentiation, while reducing Th17 activation. These changes highlight a dual potential for promoting tissue scarring while dampening inflammatory responses that could otherwise limit infection.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1679688","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:19Z","timestamp":1772775019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["miRNA\/mRNA analysis of increased TGF-\u03b2 pathways drive epithelial-mesenchymal transition and regulatory T cell differentiation"],"prefix":"10.3389","volume":"17","author":[{"given":"Toni","family":"Darville","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha V.","family":"Mokashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]},{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakash","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles W.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Pathology consultant, Michigan Diagnostic Pathologists, Henry Ford Southfield Hospital","place":["Southfield, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold C.","family":"Wiesenfeld","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh School of Medicine and the Magee-Womens Research Institute","place":["Pittsburgh, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]},{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1990.03440230060033","article-title":"The association between Chlamydia trachomatis and ectopic pregnancy. 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