Significance of Tuft Cells Expressing Hematopoietic Prostaglandin D Synthase During the Pathogenesis of Eosinophilic Chronic Rhinosinusitis

Background/Objective: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis with nasal polyps that is characterized by abundant eosinophilic infiltration within nasal polyps. Tuft cells are epithelial chemosensory cells that are present in the normal respiratory tract and activate group-2 innate lymphoid cells through their secretion of interleukin-25 and prostaglandin (PG) D2. ECRS is also characterized by the activation of group-2 innate lymphoid cells; however, the involvement of tuft cell-derived PGD2 in this process remains unclear. Methods: We selected consecutive patients with and without ECRS who underwent biopsy or surgical resection. Dual immunohistochemical analyses were performed to determine the presence of tuft cells producing PGD2, using POU class 2 transcription factor (POU2F3), a specific tuft cell marker, and hematopoietic prostaglandin D synthase (H-PGDS). Results: The cohort included 52 and 14 patients with and without ECRS, respectively. The number of total POU2F3-positive tuft cells (POU2F3+/H-PGDS+ and POU2F3+/H-PGDS−) was significantly higher in the ECRS group vs. the non-ECRS one (p < 0.0001). Moreover, the ratio of POU2F3-positive tuft cells expressing H-PGDS [POU2F3+/H-PGDS+/(POU2F3+/H-PGDS+ + POU2F3+/H-PGDS−)] was also significantly higher in the ECRS group vs. the non-ECRS one (p = 0.0084). Conclusions: These results suggest that tuft cells present in the context of ECRS may serve as a potential source of PGD2, thus involving to the amplification of type 2 inflammation.