The Roles of Orphan G Protein-Coupled Receptors in Autoimmune Diseases

G protein-coupled receptors (GPCRs) constitute the largest family of plasma membrane receptors in nature and mediate the effects of a variety of extracellular signals, such as hormone, neurotransmitter, odor, and light signals. Due to their involvement in a broad range of physiological and pathological processes and their accessibility, GPCRs are widely used as pharmacological targets of treatment. Orphan G protein-coupled receptors (oGPCRs) are GPCRs for which no natural ligands have been found, and they not only play important roles in various physiological functions, such as sensory perception, reproduction, development, growth, metabolism, and responsiveness, but are also closely related to many major diseases, such as central nervous system (CNS) diseases, metabolic diseases, and cancer. Recently, many studies have reported that oGPCRs play increasingly important roles as key factors in the occurrence and progression of autoimmune diseases. Therefore, oGPCRs are likely to become potential therapeutic targets and may provide a breakthrough in the study of autoimmune diseases. In this article, we focus on reviewing the recent research progress and clinical treatment effects of oGPCRs in three common autoimmune diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), shedding light on novel strategies for treatments.