Presence of Tuft Cells Expressing Hematopoietic Prostaglandin D Synthase in Acinar-to-Ductal Metaplasia in Human Obstructive Pancreatitis.

Acinar-to-ductal metaplasia (ADM)-a process involving the dedifferentiation or transdifferentiation of pancreatic acinar cells-is 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.