The blockade of PD-1/PD-L1 pathway promotes the apoptosis of CD19+ CD25+ Bregs and suppresses the secretion of IL-10 in patients with allergic rhinitis

Abstract

PD-1/PD-L1 pathway is crucial to immune regulation by controlling the balance between T cell tolerance and activation. However, the association between PD-1/PD-L1 pathway and regulatory B cells has not been fully investigated in allergic rhinitis. In this study, we detected the number of peripheral CD19⁺ CD25⁺ Bregs and the expression of IL-10 on this cell subset in healthy control and patients with allergic rhinitis using flow cytometry. Then, we evaluated the level of PD-L1 in CD19⁺ CD25⁺ Bregs and investigated the correlation between PD-L1 and CD4⁺ follicular T helper cells. Finally, we studied the effects of anti-PD-L1 on the apoptosis of Bregs and the production of IL-10. Comparing with healthy controls, the percentage of CD19⁺ CD25⁺ Bregs and the expression of IL-10 were both significantly decreased in AR group. In addition, the expression of PD-L1 on CD19⁺ CD25⁺ Bregs was also lower in allergic rhinitis patients. Interestingly, a negative correlation was found between the expression of PD-L1⁺ Bregs and CD4⁺ CXCR5⁺ follicular T helper cells. In vitro assay revealed that anti-PD-L1 promoted Bregs apoptosis and inhibited the expression of IL-10 in CD19⁺ CD25⁺ Bregs. Collectively, these results suggest that PD-L1 expressed on CD19⁺ CD25⁺ Bregs may be a potential regulator in the treatment of allergic rhinitis. Blockade of PD-1/PD-L1 pathway might be a valuable pathogenic target for allergic rhinitis through inhibiting the secretion of immunosuppressive cytokine and promoting CD19⁺ CD25⁺ Bregs apoptosis.

Keywords: Bregs; CD19; CD25; IL-10; PD-L1; allergic rhinitis.