The Role of Dipeptidyl-Peptidase IV in the Immune System

Dipeptidyl-peptidase IV (DPP4, also known as CD26) is a protease expressed on the cell surface. It is found in various tissues such as epithelial cells of the kidney, bile duct, liver, lungs. DPP4 can be cleaved from the cell membrane and released into plasma and other bodily fluids, maintaining its enzymatic activity and performing physiological functions in various organs and tissues. DPP4’s substrates possess unique amino acid sequences, preferring alanine or proline at the second position, and include incretin peptides, chemokines, cytokines, and neuropeptides. In this review, we explore the immunoregulatory functions of DPP4, highlighting its importance in immune response modulation and its potential as a therapeutic target for autoimmune diseases and other conditions such as type 2 diabetes. Future research should focus on elucidating the specific roles of DPP4 in various immune cell types, the temporal and spatial characteristics of DPP4 expression, unrecognized ligands for DPP4, and strategies targeting DPP4’s non-enzymatic activities. Overall, DPP4 is a promising target for autoimmune disease research, although much remains to be understood about its precise mechanisms.