{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:18:55Z","timestamp":1783343935758,"version":"3.54.6"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Autoimmune polyendocrinopathy\u2010candidiasis\u2010 ectodermal dystrophy (APECED) pathology due to autoimmune regulator (AIRE) gene mutations leads to loss of central tolerance triggering immune attack, a factor causing infertility. One of the targets of autoimmune attack is ovary and its repercussion results in polycystic ovarian syndrome (PCOS). Although reduced Tregs have been reported in PCOS, a lacunae exists on the status of <jats:italic>AIRE<\/jats:italic> gene expression and its role in treg insufficiency via HIF1A\u2010FOXP3 axis in PCOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>This is a case\u2010control cohort study recruiting 40 normal and 40 PCOS volunteers for peripheral blood sample collection and PCOS diagnoses were based on Rotterdam Consensus criteria. AIRE and <jats:italic>HIF1A<\/jats:italic> expression status was analysed by qRT PCR and western blot. FACS analyses was conducted on AIRE silenced peripheral blood mononuclear cells (PBMCs) after Treg induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results indicate a reduced <jats:italic>AIRE<\/jats:italic> (fold change log2 (RQ) = \u20132.6, <jats:italic>P<\/jats:italic> &lt; .01) and increased <jats:italic>HIF1A<\/jats:italic> (fold change log2 (RQ) = 3.6, <jats:italic>P<\/jats:italic> &lt; .02) in PBMCs of PCOS subjects compared to age\u2010matched controls. Western blot of AIRE and HIF1A corroborates with qRT PCR data. Our CHIP data demonstrate AIRE mediated <jats:italic>HIF1A<\/jats:italic> promoter regulation. Silencing of <jats:italic>AIRE<\/jats:italic> in PBMCs contributes to the upregulation of <jats:italic>HIF1A<\/jats:italic> transcripts by two\u2010fold (<jats:italic>P<\/jats:italic> &lt; .0015) and downregulation in <jats:italic>FOXP3<\/jats:italic> expression by three\u2010fold (<jats:italic>P<\/jats:italic> &lt; .0017). FACS analyses revealed that silencing of <jats:italic>AIRE<\/jats:italic> reduces Tcell to Treg conversion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our consolidated results derive a new connection among AIRE\u2010HIF1A\u2010FOXP3 with <jats:italic>AIRE<\/jats:italic> reduction enabling increased <jats:italic>HIF1A<\/jats:italic> resulting in reduced <jats:italic>FOXP3<\/jats:italic> in PBMCs of PCOS patients leading to Treg insufficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13637","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T08:01:51Z","timestamp":1666944111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Autoimmune regulator (AIRE): Takes a hypoxia\u2010inducing factor 1A (HIF1A) route to regulate FOXP3 expression in PCOS"],"prefix":"10.1111","volume":"89","author":[{"given":"Renjini Ambika","family":"Padmanabhan","sequence":"first","affiliation":[{"name":"Female Reproduction and Metabolic Syndromes Laboratory Division of Molecular Reproduction Rajiv Gandhi Centre for Biotechnology  Thycaud PO Poojappura Thiruvananthapuram Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betcy Susan","family":"Johnson","sequence":"additional","affiliation":[{"name":"Female Reproduction and Metabolic Syndromes Laboratory Division of Molecular Reproduction Rajiv Gandhi Centre for Biotechnology  Thycaud PO Poojappura Thiruvananthapuram Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay Kumar","family":"Dhyani","sequence":"additional","affiliation":[{"name":"Female Reproduction and Metabolic Syndromes Laboratory Division of Molecular Reproduction Rajiv Gandhi Centre for Biotechnology  Thycaud PO Poojappura Thiruvananthapuram Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathy M.","family":"Pillai","sequence":"additional","affiliation":[{"name":"SAMAD IVF Hospitals  V. 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Road Pattoor Thiruvananthapuram Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Jayakrishnan","sequence":"additional","affiliation":[{"name":"KJK Hospital and Fertility Research Centre  Mar Ivanios College Road Nalanchira Thiruvananthapuram Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-8932","authenticated-orcid":false,"given":"Malini","family":"Laloraya","sequence":"additional","affiliation":[{"name":"Female Reproduction and Metabolic Syndromes Laboratory Division of Molecular Reproduction Rajiv Gandhi Centre for Biotechnology  Thycaud PO Poojappura Thiruvananthapuram Kerala 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