{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:35:38Z","timestamp":1778704538254,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG064794"],"award-info":[{"award-number":["AG064794"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Aging alters immune function in women and can lead increased risk of infections, particularly in the female reproductive tract (FRT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>To determine how aging affects innate immune responses in the cervical stroma of the FRT, we isolated endocervical (CX) and ectocervical (ECX) stromal fibroblasts and determine if their expression of multiple pattern recognition receptors (PRRs) and responses to viral stimulation varied with menopause and age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Constitutive expression of most PRRs did not vary with age or menopausal status in either cell type. However, the expression of TLR7, MDA5, and NOD2 by ECX stromal fibroblasts significantly increased in post\u2010menopausal women, while the expression of NOD1 by CX stromal fibroblast also significantly increased in post\u2010menopausal women. When stratified by age, the expression of TLR6 by CX stromal fibroblasts, and MDA5 and NOD2 by ECX stromal fibroblasts increased significantly with increasing age. Stimulation with the dsRNA viral mimic HMW poly (I:C), a ligand for MDA5, resulted in significantly increased expression of the Type I interferons (IFN) IFN\u03b2 and IFN\u03b5, the Type III interferon IFN\u03bb1, and interferon\u2010stimulated genes (ISGs) MxA, OAS2, and ISG15 in both cell populations. However, upregulation of IFN\u03b2, IFN\u03bb1, MxA, OAS2, and ISG15 in response to poly (I:C) significantly declined with increasing post\u2010menopausal age in ECX stromal fibroblasts. There was no effect of age or menopause on either IFN or ISG expression in CX stromal fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, these studies demonstrate that ECX and CX fibroblasts are phenotypically distinct populations and that increasing post\u2010menopausal age reduces IFN and ISG upregulation in ECX stromal fibroblasts in response to viral stimulation, potentially leading to decreased protection against incoming viral pathogens in older post\u2010menopausal women.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70031","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T14:55:08Z","timestamp":1736261708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aging Selectively Alters PRR and ISG Expression in Endo\u2010 and Ecto\u2010Cervical Stromal Fibroblasts From the Human Female Reproductive Tract"],"prefix":"10.1111","volume":"93","author":[{"given":"Mickey V.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-2602","authenticated-orcid":false,"given":"Zheng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona D.","family":"Barr","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7549-3300","authenticated-orcid":false,"given":"Charles R.","family":"Wira","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"U. 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