{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:33:02Z","timestamp":1782876782212,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM113226"],"award-info":[{"award-number":["P20GM113226"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sphingolipids play a crucial role in gut inflammation. Neutral ceramidase (NcDase) serves as a pivotal regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of intestinal epithelial cells (IEC) NcDase to colitis is not well understood. Here, a protective mechanism by which IEC NcDase deficiency (\n                    <jats:italic>Asah2<\/jats:italic>\n                    <jats:sup>\u0394IEC<\/jats:sup>\n                    ) and its\u2010related gangliosides prevent dextran sulfate sodium (DSS)\u2010induced colitis in mice is described.\n                    <jats:italic>Asah2<\/jats:italic>\n                    <jats:sup>\u0394IEC<\/jats:sup>\n                    mice display reduced susceptibility to DSS\u2010induced colitis and increase regulatory T (T\n                    <jats:sub>reg<\/jats:sub>\n                    ) cells compared to\n                    <jats:italic>Asah2<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    littermates. Deletion of IEC NcDase induces the upregulation of sialyltransferase ST8SIA1 and promotes the sialic\u2010acid\u2010containing ganglioside GD3 production. Siglec\u2010E is a sialic\u2010acid\u2010binding lectin expresses predominantly on myeloid cells. Mechanistically, it is identified that GD3 is a functional ligand for Siglec\u2010E on macrophages and found that GD3\/Siglec\u2010E interaction\u00a0induced a rapid metabolic rewiring of macrophages that involved the production of IL\u201033, which contributes to the generation of ST2\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>reg<\/jats:sub>\n                    \u00a0cells. Finally, deletion of ST8SIA1 or administration of dietary GD3 induces or reduces mucosal inflammation, respectively. This work defines a critical role for ganglioside GD3 in the induction of colonic T\n                    <jats:sub>reg<\/jats:sub>\n                    cells and identifies an activating pathway that follows engagement of Siglec\u2010E.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512681","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T11:58:53Z","timestamp":1762516733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intestinal Neutral Ceramidase Deficiency Triggers Regulatory T Cell Response via Gd3 to Protect the Host from Intestinal Inflammation"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhishan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 USA"},{"name":"Department of Immunology School of Basic Medical Sciences Xinxiang Medical University  Xinxiang 453003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh K","family":"Sriwastva","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanguli","family":"Tuohongerbieke","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Noud","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Immunotherapy University of Louisville Louisville KY 40202 USA"},{"name":"Brown Cancer Center University of Louisville Louisville KY 40202 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