[Dysfunctions of the CXCL12 (SDF-1)/CXCR4 signaling axis in the WHIM syndrome and the idiopathic CD4(+) T-cell lymphocytopenia]

Abstract

Chemokines are small cytokine-like secreted proteins that govern migration of leukocytes to their specific niches in lymphoid organs and to inflammatory sites. They mediate their functions by binding to and activating chemokine receptors, which belong to the heptahelical G protein-coupled receptor family. The CXC chemokine Stromal cell Derived Factor-1 (SDF-1/CXCL12) is the sole natural ligand for the broadly expressed CXCR4 receptor and acts as a chemoattractant for many leukocyte subsets. The CXCL12/CXCR4 axis exerts critical activities in homeostatic processes such as organogenesis, hematopoiesis and leukocyte trafficking. Dysregulations of CXCR4 signaling and/or expression are associated with several infectious, inflammatory, autoimmune and malignant conditions. In light of recent data, we review here CXCR4 dysfunctions unveiled in two rare human immunodeficiency disorders, one characterized by a gain of CXCR4 function, the WHIM syndrome, and the other by a loss of CXCR4 function, the idiopathic CD4(+) T-cell lymphocytopenia.