CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation

Dipeptidylpeptidase IV/CD26 is expressed on the surface of various cell types. Through its enzymatic activity, its major function is to cleave the N-terminal dipeptide from diverse molecules including members of the chemokine family of cytokines. The N-terminus of these chemokines is important for activation of and binding to seven-transmembrane G-protein linked chemokine receptors, and early studies showed truncation by CD26 physiologically alters these properties of select chemokines resulting in diverse functional outcomes. Stromal-derived factor-1 (SDF-1/CXCL12), a chemokine involved in hematopoietic cell chemotaxis, homing, mobilization and survival, is cleaved by CD26 producing a form that is inactive in CXCR4 signaling and has some antagonistic properties in vitro. Recent studies have shown that the inhibition of cell-surface CD26 peptidase activity on hematopoietic stem/progenitor cell (HSC/HPC) populations increases their SDF-1/CXCL12 directed chemotaxis in vitro, and in vivo homing and engraftment. CD26 inhibition may, therefore, represent a novel approach to increasing the efficacy and success of HSC/HPC transplantation, especially under conditions of limiting donor cell yield.