{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:58:22Z","timestamp":1788357502537,"version":"build-2803163510"},"reference-count":85,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:p>\n                    Upon injury, epithelial-derived IL-18 is released and induces an inflammatory response in underlying IL18R1\n                    <jats:sup>+<\/jats:sup>\n                    lamina propria cells. Notably,\n                    <jats:italic toggle=\"yes\">Il18r1<\/jats:italic>\n                    is also predicted to be expressed and functional in intestinal epithelial cells (IECs), since epithelial IL18R1 deficiency contributes to worsened outcomes upon inflammatory challenge. However, the nature of\n                    <jats:italic toggle=\"yes\">\n                      Il18r1\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    IECs, and their subsequent role in epithelial-intrinsic IL-18 signaling is poorly characterized. Here, we show that, in the murine small intestine, the IL-18 receptor is expressed by rare IECs that we identified to be a subset of enterochromaffin cells (ECC). While these cells are the major producers of serotonin in the intestine, we found no evidence that IL-18 regulated serotonin metabolism or release. Rather, upon radiation-induced injury,\n                    <jats:italic toggle=\"yes\">\n                      Il18r1\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    cells appeared in the crypt base and took on a revival stem cell (revSC) program, marked by mixed expression of YAP\/TAZ and enteroendocrine genes signatures. Functionally, irradiated\n                    <jats:italic toggle=\"yes\">\n                      Il18\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice display reduced epithelial proliferation and altered differentiation in the small intestine, characterized by increased Paneth cells (PC) and elevated\n                    <jats:italic toggle=\"yes\">Wnt3<\/jats:italic>\n                    levels, which was partially recapitulated in\n                    <jats:italic toggle=\"yes\">\n                      Il18\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ileal organoids. In sum, we identified an\n                    <jats:italic toggle=\"yes\">Il18r1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    population in the epithelium and revealed a role for IEC-intrinsic IL-18 signaling during injury.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2417149122","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:23:38Z","timestamp":1748348618000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4984-3012","authenticated-orcid":false,"given":"Nathaniel J.","family":"Winsor","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto","place":["ON, Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek K.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto","place":["ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Ranger","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ojas","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["ON, 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