{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:20:41Z","timestamp":1785403241550,"version":"3.56.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,6,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <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 toggle=\"yes\">\n                        Ifn\u03b5\n                        <jats:sup>\u2212\/\u2212<\/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 toggle=\"yes\">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 toggle=\"yes\">in vivo<\/jats:italic>\n                      , where it sustains inflammatory enterocyte subsets and maintains type III IFN expression. Loss of\n                      <jats:italic toggle=\"yes\">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>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>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. In this manuscript, we define the epithelial cell types that constitutively express IFN\u03b5 in the uterus and small intestine at a single-cell resolution. We show that mice lacking IFN\u03b5 lose key antiviral defenses in a tissue-dependent manner; uterine epithelial cells have diminished basal ISG expression, and key populations of cytokine-expressing enterocytes are absent from the small intestine. In the intestine, this correlates with increased susceptibility to infection with an enteric virus in mice. These findings establish IFN\u03b5 as a key contributor to mucosal immunity, sustaining antiviral defenses within tissue-specific epithelial cells of both the female reproductive tract and intestine, and broaden our understanding of its role beyond traditional pathogen-induced interferon responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00340-26","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:01:16Z","timestamp":1777986076000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Constitutive interferon epsilon expression shapes antiviral epithelial states in the female reproductive tract and intestine"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-6947","authenticated-orcid":true,"given":"Rebecca L.","family":"Casazza","sequence":"first","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1380-8551","authenticated-orcid":true,"given":"Samantha","family":"Skavicus","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Duke University School of Medicine","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-3559","authenticated-orcid":false,"given":"David","family":"Hare","sequence":"additional","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4137-1310","authenticated-orcid":false,"given":"Kaila A.","family":"Cooley","sequence":"additional","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5307-3428","authenticated-orcid":true,"given":"Nicholas S.","family":"Heaton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Duke University School of Medicine","place":["Durham, USA"]},{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke Human Vaccine Institute","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-6309","authenticated-orcid":true,"given":"Carolyn B.","family":"Coyne","sequence":"additional","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine","place":["Durham, USA"]},{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke Human Vaccine Institute","place":["Durham, 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