{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:10:07Z","timestamp":1760145007054,"version":"build-2065373602"},"reference-count":85,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01 AR064418","R01 AI146042","R35 GM136233"],"award-info":[{"award-number":["R01 AR064418","R01 AI146042","R35 GM136233"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Crohn\u2019s disease is a chronic, debilitating, inflammatory bowel disease. Here, we report a critical role of phospholipase C-\u03b23 (PLC-\u03b23) in intestinal homeostasis. In PLC-\u03b23-deficient mice, exposure to oral dextran sodium sulfate induced lethality and severe inflammation in the small intestine. The lethality was due to PLC-\u03b23 deficiency in multiple non-hematopoietic cell types. PLC-\u03b23 deficiency resulted in reduced Wnt\/\u03b2-catenin signaling, which is essential for homeostasis and the regeneration of the intestinal epithelium. PLC-\u03b23 regulated the Wnt\/\u03b2-catenin pathway in small intestinal epithelial cells (IECs) at transcriptional, epigenetic, and, potentially, protein\u2013protein interaction levels. PLC-\u03b23-deficient IECs were unable to respond to stimulation by R-spondin 1, an enhancer of Wnt\/\u03b2-catenin signaling. Reduced expression of PLC-\u03b23 and its signature genes was found in biopsies of patients with ileal Crohn\u2019s disease. PLC-\u03b2 regulation of Wnt signaling was evolutionally conserved in Drosophila. Our data indicate that a reduction in PLC-\u03b23-mediated Wnt\/\u03b2-catenin signaling contributes to the pathogenesis of ileal Crohn\u2019s disease.<\/jats:p>","DOI":"10.3390\/cells13110986","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T11:50:09Z","timestamp":1717588209000},"page":"986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ileal Crohn\u2019s Disease Exhibits Reduced Activity of Phospholipase C-\u03b23-Dependent Wnt\/\u03b2-Catenin Signaling Pathway"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8548-4424","authenticated-orcid":false,"given":"Tomoaki","family":"Ando","sequence":"first","affiliation":[{"name":"Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla, CA 92037, USA"},{"name":"Atopy Research Center, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5806","authenticated-orcid":false,"given":"Ikuo","family":"Takazawa","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary T.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology and the Dartmouth Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2903-2332","authenticated-orcid":false,"given":"Ryoji","family":"Ito","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla, CA 92037, USA"},{"name":"Central Institute for Experimental Animals, Kawasaki 210-0821, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Tomimori","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1918-9216","authenticated-orcid":false,"given":"Zbigniew","family":"Mikulski","sequence":"additional","affiliation":[{"name":"Imaging Facility, La Jolla Institute for Immunology, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, 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