G-Protein-Coupled Receptor GPR65 Potentially Reduces Innate Lymphoid Cell-Related Type 2 Inflammation in Airway and Lung

Group 2 innate lymphoid cells (ILC2s) promote asthma by releasing type 2 cytokines that promote allergic-type inflammation. As a subset of innate lymphoid cells (ILCs), ILC2s are activated by alarmin cytokines released by airway epithelial cells when exposed to an allergen. Previous studies examining the role of G-protein-coupled receptor (GPR65) during an inflammatory response have identified its role as an activator of intracellular signaling pathways. However, the role of GPR65 on ILC2 function in ILC2-driven type 2 lung inflammation is unknown. To determine the role of GPR65 in an allergic asthma response, GPR65 knock-out (GPR65-/-) mice and Wild Type (WT) mice were challenged with Alternaria to observe the differences in lung inflammation and ILCs by flow cytometry and the differences in type 2 cytokines by enzyme-linked immunosorbent assay (ELISA). Our data shows that GPR65-/- mice have trending increases in airway and lung inflammation, proliferation of ILCs, and airway type 2 cytokines compared to WT mice. These preliminary findings suggest that GPR65 may suppress the activation of ILCs after exposure to Alternaria. Therefore, GPR65 may serve a protective role in type 2 lung inflammation and allergic airway disease