{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:57:41Z","timestamp":1790128661999,"version":"4.0.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21gm1010004"],"award-info":[{"award-number":["21gm1010004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"a Grant-in-Aid for Scientific Research","award":["JP21H050430"],"award-info":[{"award-number":["JP21H050430"]}]},{"name":"a Grant-in-Aid for Scientific Research","award":["21H02747"],"award-info":[{"award-number":["21H02747"]}]},{"name":"a Grant-in-Aid for Scientific Research","award":["22gm6210016"],"award-info":[{"award-number":["22gm6210016"]}]},{"DOI":"10.13039\/100016980","name":"Otsuka Toshimi Scholarship Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016980","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14\u2212\/\u2212 mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14\u2212\/\u2212 mice that received P2ry14-deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1\/2 signaling. Thus, the UDP-glucose\/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils.<\/jats:p>","DOI":"10.1093\/intimm\/dxad050","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:11:34Z","timestamp":1702908694000},"page":"155-166","source":"Crossref","is-referenced-by-count":12,"title":["The UDP-glucose\/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation"],"prefix":"10.1093","volume":"36","author":[{"given":"Li","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4552-783X","authenticated-orcid":false,"given":"Daisuke","family":"Okuzaki","sequence":"additional","affiliation":[{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka , Japan"},{"name":"Genome Information Research Center, Research Institute for Microbial Diseases, Osaka 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazuki","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ogino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Nakamura","sequence":"additional","affiliation":[{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka , Japan"},{"name":"Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University , Suita, Osaka , Japan"},{"name":"Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University , Suita, Osaka , Japan"},{"name":"Center for Infectious Disease Education and Research, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka , Japan"},{"name":"Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University , Suita, Osaka , Japan"},{"name":"Center for Infectious Disease Education and Research, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisako","family":"Kayama","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University , Suita, Osaka , Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka , Japan"},{"name":"Institute for Advanced Co-Creation Studies, Osaka University , Suita, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"2024030909590174300_CIT0001","first-page":"74","article-title":"Ulcerative colitis","volume-title":"Nat Rev Dis Primers","author":"Kobayashi","year":"2020"},{"key":"2024030909590174300_CIT0002","first-page":"205","article-title":"Epidemiology and risk factors for IBD","volume-title":"Nat Rev Gastroenterol Hepatol","author":"Ananthakrishnan","year":"2015"},{"key":"2024030909590174300_CIT0003","first-page":"573","article-title":"Gut microbiota and IBD: causation or correlation","volume-title":"Nat Rev Gastroenterol 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in murine models","volume-title":"JGH Open","author":"Kogure","year":"2020"},{"key":"2024030909590174300_CIT0033","first-page":"3159","article-title":"Purinergic P2Y(1)(4) receptor modulates stress-induced hematopoietic stem\/progenitor cell senescence","volume-title":"J Clin Invest","author":"Cho","year":"2014"},{"key":"2024030909590174300_CIT0034","first-page":"1592","article-title":"P2Y-like receptor, GPR105 (P2Y14), identifies and mediates chemotaxis of bone-marrow hematopoietic stem cells","volume-title":"Genes Dev","author":"Lee","year":"2003"},{"key":"2024030909590174300_CIT0035","first-page":"e13391","article-title":"Targeting eotaxin-1 and CCR3 receptor alleviates enteric neuropathy and colonic dysfunction in TNBS-induced colitis in guinea pigs","volume-title":"Neurogastroenterol Motil","author":"Filippone","year":"2018"},{"key":"2024030909590174300_CIT0036","doi-asserted-by":"crossref","first-page":"7780","DOI":"10.3390\/ijms23147780","article-title":"Potent CCR3 receptor 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