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VIP and PACAP as Regulators of Immunity: New Perspectives from A Receptor Point of View

Catalina Abad and Yossan-Var Tan

Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) are two neuropeptides acting through three common G-protein coupled receptors (VPAC1, VPAC2 and PAC1). Among their pleiotropic actions within the organism, VIP and PACAP are known to exhibit immunomodulatory properties in both the innate and adaptive immune axes. The fact that they inhibit inflammation in murine models of disease has brought these peptides into the spotlight within the field of therapeutic discovery for autoimmune/inflammatory diseases. Pharmacological tools and transgenic mice have been useful in order to investigate the involvement of each of their three receptors in these actions. This review focuses on the relevance of the VPAC2 receptor on VIP and PACAP modulation of immune responses, and discusses its potential as a target for the treatment of Th1-driven inflammatory disorders.