{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:06:20Z","timestamp":1780459580566,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Osaka Medical and Pharmaceutical University Internal Research Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Acinar-to-ductal metaplasia (ADM)\u2014a process involving the dedifferentiation or transdifferentiation of pancreatic acinar cells\u2014is recognized as an initial event in pancreatic tumorigenesis. Studies in mouse models have revealed that tuft cells, which are chemosensory epithelial cells, appear in ADM following tissue injury, and tuft cell-produced prostaglandin (PG) D2 may suppress inflammation and tumorigenesis. However, the presence and role of tuft cells in the human pancreas remain unclear. Therefore, in this study, we investigated the presence of tuft cells and PGD2 production in human ADM. We analyzed ADM lesions from consecutive patients undergoing surgical resection for pancreatic tumors using dual immunohistochemical staining for POU domain class 2 transcription factor 3 (POU2F3) and hematopoietic PGD synthase (H-PGDS). All 29 patients (13 men and 16 women) with diagnoses including pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms exhibited ADM in regions of obstructive pancreatitis. Immunohistochemical analysis showed that 67.3% of ADM lesions contained POU2F3- and\/or H-PGDS-positive cells. Among these, 85.5% of POU2F3-positive cells co-expressed H-PGDS, and 76.2% of H-PGDS-positive cells were POU2F3-positive. These findings indicate that tuft cells present in human ADM produce PGD2, suggesting a role in tissue repair. Tuft cells may represent a potential therapeutic target in pancreatitis, warranting further investigation into their functional role in ADM.<\/jats:p>","DOI":"10.3390\/cimb48060585","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Presence of Tuft Cells Expressing Hematopoietic Prostaglandin D Synthase in Acinar-to-Ductal Metaplasia in Human Obstructive Pancreatitis"],"prefix":"10.3390","volume":"48","author":[{"given":"Kenta","family":"Hosomi","sequence":"first","affiliation":[{"name":"Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1, Nasahara, Takatsuki City 569-1094, Osaka, Japan"},{"name":"Department of Pathology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuaki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"},{"name":"Division of Pathology, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"},{"name":"Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-1370","authenticated-orcid":false,"given":"Kohei","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Center for Medical Research & Development, Division of Translational Research, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tomioka","sequence":"additional","affiliation":[{"name":"Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Asakuma","sequence":"additional","affiliation":[{"name":"Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-0655","authenticated-orcid":false,"given":"Sang-Woong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-0769","authenticated-orcid":false,"given":"Ko","family":"Fujimori","sequence":"additional","affiliation":[{"name":"Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1, Nasahara, Takatsuki City 569-1094, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"},{"name":"Division of Pathology, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-Machi, Takatsuki City 569-8686, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez Gil, Y., Jim\u00e9nez S\u00e1nchez, P., Mu\u00f1oz Velasco, R., Garc\u00eda Garc\u00eda, A., and S\u00e1nchez-Ar\u00e9valo Lobo, V.J. (2021). Molecular alterations in pancreatic cancer: Transfer to the clinic. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042077"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Marstrand-Dauc\u00e9, L., Lorenzo, D., Chassac, A., Nicole, P., Couvelard, A., and Haumaitre, C. (2023). Acinar-to-ductal metaplasia (ADM): On the road to pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129946"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.jcmgh.2021.11.010","article-title":"On the origin of pancreatic cancer: Molecular tumor subtypes in perspective of exocrine cell plasticity","volume":"13","author":"Backx","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nrgastro.2017.12","article-title":"Acinar cell plasticity and development of pancreatic ductal adenocarcinoma","volume":"14","author":"Storz","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1136\/gut.2010.225920","article-title":"Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis","volume":"60","author":"Pinho","year":"2011","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/BF01536153","article-title":"Histochemical and ultrastructural characteristics of tubular complexes in human acute pancreatitis","volume":"34","author":"Willemer","year":"1989","journal-title":"Dig. Dis. Sci."},{"key":"ref_7","first-page":"1285","article-title":"Ductal metaplasia of human exocrine pancreas and its association with carcinoma","volume":"45","author":"Parsa","year":"1985","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2007.09.009","article-title":"In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation in inflammatory ductal metaplasia","volume":"133","author":"Strobel","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1053\/j.gastro.2020.07.037","article-title":"Tuft cells inhibit pancreatic tumorigenesis in mice by producing prostaglandin D2","volume":"159","author":"DelGiorno","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1007\/s00018-012-0984-7","article-title":"The intestinal epithelium tuft cells: Specification and function","volume":"69","author":"Gerbe","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.coi.2020.09.006","article-title":"Tuning tuft cells: New ligands and effector functions reveal tissue-specific function","volume":"68","author":"Billipp","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1101\/gad.314815.118","article-title":"POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer","volume":"32","author":"Huang","year":"2018","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41577-019-0176-x","article-title":"Regulation of immune responses by tuft cells","volume":"19","author":"Schneider","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-pathol-042320-112212","article-title":"Tuft cells: Context- and tissue-specific programming for a conserved cell lineage","volume":"18","author":"Kotas","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"DelGiorno, K.E., Naeem, R.F., Fang, L., Chung, C.Y., Ramos, C., Luhtala, N., O\u2019Connor, C., Hunter, T., Manor, U., and Wahl, G.M. (2020). Tuft cell formation reflects epithelial plasticity in pancreatic injury: Implications for modeling human pancreatitis. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00088"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1053\/j.gastro.2021.10.027","article-title":"Single-cell transcriptomics reveals a conserved metaplasia program in pancreatic injury","volume":"162","author":"Ma","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.plipres.2017.04.003","article-title":"Prostaglandin synthases: Molecular characterization and involvement in prostaglandin biosynthesis","volume":"66","author":"Seo","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Urade, Y. (2021). Biochemical and structural characteristics, gene regulation, physiological, pathological and clinical features of lipocalin-type prostaglandin D2 synthase as a multifunctional lipocalin. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.718002"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0952-3278(03)00077-2","article-title":"Hematopoietic prostaglandin D synthase","volume":"69","author":"Kanaoka","year":"2003","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/glia.21128","article-title":"Expression and detrimental role of hematopoietic prostaglandin D synthase in spinal cord contusion injury","volume":"59","author":"Redensek","year":"2011","journal-title":"Glia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/00006676-200307000-00009","article-title":"The PPARgamma ligand, 15d-PGJ2, attenuates the severity of cerulein-induced acute pancreatitis","volume":"27","author":"Hashimoto","year":"2003","journal-title":"Pancreas"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1053\/j.gastro.2020.11.010","article-title":"Single-nucleus and in situ RNA\u2013sequencing reveal cell topographies in the human pancreas","volume":"160","author":"Tosti","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nakanishi, K., Ishida, M., Taniguchi, K., Hosomi, K., Arima, J., Tomioka, A., Asakuma, M., Miyamoto, Y., Fujimori, K., and Hirose, Y. (2025). Immunohistochemical demonstration of tuft cells in human acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Biomedicines, 13.","DOI":"10.3390\/biomedicines13081944"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3892\/mmr.2025.13624","article-title":"Differential expression of haematopoietic prostaglandin D synthase by POU2F3-positive tuft cells in conventional bilayered oncocytic and metaplastic epithelia of Warthin tumours","volume":"32","author":"Hosomi","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/glia.10183","article-title":"Hematopoietic prostaglandin D synthase is expressed in microglia in the developing postnatal mouse brain","volume":"42","author":"Mohri","year":"2003","journal-title":"Glia"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yamada, Y., Simon, R., Iwane, K., Nakanishi, Y., Takeuchi, Y., Yoshizawa, A., Takada, M., Toi, M., Haga, H., and Marx, A. (2023). An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: The possible relationship of SOX9. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10949-5"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1210\/jc.2005-1982","article-title":"Gestational age-dependent up-regulation of prostaglandin D synthase (PGDS) and production of PGDS-derived antiinflammatory prostaglandins in human placenta","volume":"91","author":"Helliwell","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S191","DOI":"10.1038\/sj.bjp.0707488","article-title":"The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses","volume":"153","author":"Pettipher","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1002\/eji.202048909","article-title":"Prostaglandin regulation of type 2 inflammation: From basic biology to therapeutic interventions","volume":"51","author":"Oyesola","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1084\/jem.193.2.255","article-title":"Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2","volume":"193","author":"Hirai","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"110298","DOI":"10.1016\/j.clim.2024.110298","article-title":"Roles of prostaglandins in immunosuppression","volume":"265","author":"Luo","year":"2024","journal-title":"Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"503128","DOI":"10.1155\/2012\/503128","article-title":"PGD synthase and PGD2 in immune response","volume":"2012","author":"Joo","year":"2012","journal-title":"Mediat. Inflam."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.17305\/bb.2024.10485","article-title":"Advances in PGD2\/PTGDR2 signaling pathway in tumors: A review","volume":"24","author":"Tian","year":"2024","journal-title":"Biomol. Biomed."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2019.02.003","article-title":"Tuft cells: From the mucosa to the thymus","volume":"210","author":"Nevo","year":"2019","journal-title":"Immunol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17466","DOI":"10.1038\/s41598-019-53997-3","article-title":"Distribution pattern and molecular signature of cholinergic tuft cells in human gastro-intestinal and pancreatic-biliary tract","volume":"9","author":"Ruppert","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1080\/14728222.2020.1841168","article-title":"Tuft cells: An emerging therapeutic target for pancreatitis and pancreatic cancer?","volume":"24","author":"Yang","year":"2020","journal-title":"Expert Opin. Ther. Targets"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/6\/585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:58:48Z","timestamp":1780459128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/6\/585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cimb48060585"],"URL":"https:\/\/doi.org\/10.3390\/cimb48060585","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]}}}