Dipeptidyl peptidase 4 (DPP4, CD26) is a protease that cleaves selected amino acids at the N-terminal penultimate position and has the potential to alter the protein function. The regulation and roles of DPP4 activity are not well understood; therefore, the purpose of this review is to discuss the recent literature regarding DPP4 regulation, as well as the variety of molecules it may affect, and their potential clinical applications.
Recent insight into the number of proteins that have DPP4 sites, and how DPP4 truncation may alter hematopoiesis based on the protein full length vs. truncated state, has shown that DPP4 truncation of colony-stimulating factors (CSFs) alters their function and that the activity of these CSFs can be enhanced when DPP4 activity is inhibited. DPP4 inhibition has recently been used in a clinical trial to attempt to enhance the engraftment of cord blood cells, and an endogenous DPP4 inhibitor tissue factor pathway inhibitor has been discovered, increasing our understanding of the potential importance of DPP4.
DPP4 plays a role in regulating the activity of CSFs and other cytokines involved in hematopoiesis. This information may be useful for enhancing hematopoietic cell transplantation, blood cell recovery after stress, and for understanding the physiology and pathophysiology of blood and other cell systems.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA
*These authors contributed equally to this work and are considered co-first authors.
Correspondence to Hal E. Broxmeyer, PhD, Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, R2-302, Indianapolis, IN 46202-5181 USA. Tel: +1 317 274 7510; fax: +1 317 274 7592; e-mail: firstname.lastname@example.org