{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:19:36Z","timestamp":1791771576807,"version":"4.3.4"},"posted":{"date-parts":[[2024,11,17]]},"group-title":"Immunology","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Antiviral defenses at mucosal barriers are essential for preventing viral entry and systemic infection. Interferon epsilon (IFN\u03b5) is a unique type I IFN that, unlike other family members, is not induced by infection but is constitutively expressed in epithelial tissues. IFN\u03b5 was initially characterized in the female reproductive tract (FRT), where it provides broad antiviral protection, but its roles outside the FRT remain poorly defined. Here, we used\n                  <jats:italic>\n                    Ifn\u03b5\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice and single-cell RNA sequencing to delineate IFN\u03b5 function across distinct mucosal surfaces. In the FRT,\n                  <jats:italic>Ifn\u03b5<\/jats:italic>\n                  expression was restricted to specific epithelial subsets, was independent of estrous stage, and maintained basal ISG expression. IFN\u03b5 was also retained intracellularly in primary human FRT-derived cells. Extending these analyses to the intestine, we found that IFN\u03b5 is highly expressed in villous-tip enterocytes of the small intestine\n                  <jats:italic>in vivo<\/jats:italic>\n                  , where it sustains inflammatory enterocyte subsets and maintains type III IFN expression. Loss of\n                  <jats:italic>Ifn\u03b5<\/jats:italic>\n                  depleted these subsets and rendered mice more susceptible to enteric viral infection. Together, these findings establish IFN\u03b5 as a constitutively expressed, spatially restricted IFN that coordinates mucosal antiviral defenses across both reproductive and gastrointestinal epithelial tissues.\n                <\/jats:p>","DOI":"10.1101\/2024.11.15.623843","type":"posted-content","created":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T22:15:19Z","timestamp":1731881719000},"source":"Crossref","is-referenced-by-count":1,"title":["Constitutive Interferon Epsilon Expression Shapes Antiviral Epithelial States in the Female Reproductive Tract and Intestine"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-6947","authenticated-orcid":false,"given":"Rebecca L.","family":"Casazza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Skavicus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaila A.","family":"Cooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5307-3428","authenticated-orcid":false,"given":"Nicholas S.","family":"Heaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-6309","authenticated-orcid":false,"given":"Carolyn B.","family":"Coyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025092412001378000_2024.11.15.623843v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110438"},{"key":"2025092412001378000_2024.11.15.623843v2.2","doi-asserted-by":"crossref","unstructured":"Bourke, N.M. , S.L. Achilles , S.U. Huang , H.E. Cumming , S.S. Lim , I. Papageorgiou , L.J. Gearing , R. Chapman , S. Thakore , N.E. Mangan , S. Mesiano , and P.J. Hertzog . 2022. Spatiotemporal regulation of human IFN-epsilon and innate immunity in the female reproductive tract. JCI Insight 7:","DOI":"10.1172\/jci.insight.135407"},{"key":"2025092412001378000_2024.11.15.623843v2.3","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1016\/j.jcmgh.2022.02.007","article-title":"A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics","volume":"13","year":"2022","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"2025092412001378000_2024.11.15.623843v2.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035538"},{"key":"2025092412001378000_2024.11.15.623843v2.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010843"},{"key":"2025092412001378000_2024.11.15.623843v2.6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jcmgh.2023.10.006","article-title":"Epithelially Restricted Interferon Epsilon Protects Against Colitis","volume":"17","year":"2024","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"2025092412001378000_2024.11.15.623843v2.7","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3A0214-088RRR"},{"key":"2025092412001378000_2024.11.15.623843v2.8","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/s41598-024-51261-x","article-title":"An RNA-Seq analysis of coronavirus in the skin of the Pangolin","volume":"14","year":"2024","journal-title":"Sci Rep"},{"key":"2025092412001378000_2024.11.15.623843v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.11.016"},{"key":"2025092412001378000_2024.11.15.623843v2.10","doi-asserted-by":"publisher","DOI":"10.1080\/10985549.2024.2366207"},{"key":"2025092412001378000_2024.11.15.623843v2.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233321"},{"key":"2025092412001378000_2024.11.15.623843v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.123"},{"key":"2025092412001378000_2024.11.15.623843v2.13","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"2025092412001378000_2024.11.15.623843v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-023-01767-Y"},{"key":"2025092412001378000_2024.11.15.623843v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2004.03.003"},{"key":"2025092412001378000_2024.11.15.623843v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.08.002"},{"key":"2025092412001378000_2024.11.15.623843v2.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814597116"},{"key":"2025092412001378000_2024.11.15.623843v2.18","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41590-025-02155-1","article-title":"Bat organoids reveal antiviral responses at epithelial surfaces","volume":"26","year":"2025","journal-title":"Nat Immunol"},{"key":"2025092412001378000_2024.11.15.623843v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2025092412001378000_2024.11.15.623843v2.20","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01043-13"},{"key":"2025092412001378000_2024.11.15.623843v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.025"},{"key":"2025092412001378000_2024.11.15.623843v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27729-z"},{"key":"2025092412001378000_2024.11.15.623843v2.23","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2025092412001378000_2024.11.15.623843v2.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2019.101328"},{"key":"2025092412001378000_2024.11.15.623843v2.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06421-w"},{"key":"2025092412001378000_2024.11.15.623843v2.26","doi-asserted-by":"crossref","unstructured":"Martinez-Espinoza, I. , P.I. 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