Protease-activated Receptor-2 Suppresses Interleukin (IL)-10 Expression in B Cells Via Upregulating Bcl2L12 in Patients with Allergic Rhinitis

Background And Aims: The function of interleukin (IL)-10-producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.

Methods: Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2-like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.

Results: We observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the capability of IL-10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.

Conclusions: Activation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.