Prostaglandin E2 signal inhibits T regulatory cell differentiation during allergic rhinitis inflammation through EP4 receptor.

Objective: Allergic rhinitis (AR) is a common disease seriously affecting quality of life, and until now the effect of medical therapy is not satisfactory. It is essential to explore in depth the pathologic mechanism of AR to offer new ideas for developing novel treatment strategies. The defect of T regulatory (Treg) cells plays a critical role in the pathogenesis of AR, but the underlying mechanism remains to be elucidated. This study aims to determine the effect of Prostaglandin E2 (PGE2) on the differentiation of Treg cells in AR patients and the involvement of E prostanoid (EP) receptor signaling pathway. Methods: The proportion of Treg cells and the level of PGE2 in the peripheral blood of AR patients and healthy controls were compared. Differentiation rate of Treg cells under the influence of various concentrations of PGE2 with or without diverse EP receptor agonists and antagonists were investigated through cell culture and flow cytometry in vitro. The cyclic AMP (cAMP) mimic or protein kinase B (Akt) inhibitor was also added to the culture to evaluate the downstream pathway of EP receptor signaling. Results: The proportion of Treg cells decreased and PGE2 concentration increased in the peripheral blood of AR patients compared to healthy controls. PGE2 dose-dependently suppressed the differentiation of Treg cells from both human and mice naive CD4(+) T cells in vitro. This inhibitory effect was mediated through EP4 via a mechanism involving activation of cAMPdependent proteinkinase A (PKA) signaling pathway. Conclusion: PGE2-EP4-cAMP signaling might mediate the development of AR by inhibiting the differentiation of Treg cells.