GPR65, a Potential Therapeutic Target for Th17-mediated Autoimmune Diseases, is Regulated by the CREB/CRTC2 Pathway

Abstract The cAMP response element-binding (CREB) protein has emerged as an important regulator of immune function. We have previously shown that CREB, along with its co-activator CRTC2, modulates autoimmune disease by promoting differentiation of the pro-inflammatory T cell, Th17. Th17 cells have been linked to the development of autoimmune diseases including multiple sclerosis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, and asthma. The CREB pathway is induced by a variety of inflammatory signals, growth factors, and hormones that leads to the transcription of genes with cAMP-response elements. Through RNAseq, we identified multiple genes that may be regulated by CREB in Th17 cells. Here we show that the G-Protein-Coupled Receptor (GPCR), GPR65 is highly expressed in Th17 cells and is regulated by the CREB/CRTC2 pathway. The development of GPR65 antagonists may be a novel therapeutic avenue for the treatment of Th17-mediated autoimmune diseases.