The G-Protein–Coupled Receptor ALX/Fpr2 Regulates Adaptive Immune Responses in Mouse Submandibular Glands

Abstract ALX/FPR2 is a G-protein–coupled receptor that has multiple binding partners, including the endogenous lipid mediators resolvin D1 (RvD1), lipoxin A 4 (LXA 4 ), and the Ca 2+ -dependent phospholipid-binding protein Annexin A1. Previous studies demonstrated that RvD1 activates ALX/FPR2 to resolve salivary gland inflammation in the NOD/ShiLtJ mouse model for Sjogren's syndrome. Moreover, mice lacking the ALX/FPR2 display an exacerbated salivary gland inflammation in response to lipopolysaccharide. Additionally, activation of ALX/FPR2 has been shown to be important for regulating antibody production in B cells. The above studies indicate that ALX/FPR2 promotes resolution of salivary gland inflammation while modulating adaptive immunity, suggesting the need for investigation of the role of ALX/FPR2 in regulating antibody production and secretory function in mouse salivary glands. Our results indicate that aging female KO mice lacking the ALX/FPR2 display a significant reduction of saliva flow rates and weight loss, an increased expression of autoimmune-associated genes, an up-regulation of autoantibody production, and increased CD20-positive B cell population. Although not all effects were noted among the male KO mice, the results nonetheless indicate that ALX/FPR2 is clearly involved in the adaptive immunity and secretory function in salivary glands, with further investigation warranted to determine the cause(s) of sexual differences noted above.