Regulation of hematopoiesis by cxcl12/cxcr4 signaling

Abstract

CXCL12 (stromal-derived factor 1, SDF-1) is a chemokine that is constitutively expressed at high levels in the bone marrow and is a key component of the stem cell niche. Its major receptor CXCR4 is broadly expressed on hematopoietic cells, including hematopoietic stem cells (HSCs). The CXCL12/CXCR4 axis plays a key role in regulating many aspects of hematopoiesis. It is essential for normal B-cell lymphopoiesis and is a key determinant of neutrophil release from the bone marrow. Activating mutations of CXCR4 are causative of the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, which is characterized by abnormal neutrophil retention in the bone marrow and impaired B-cell development. The CXCL12/CXCR4 axis also plays an essential role in HSC maintenance and trafficking, and pharmaceuticals that inhibit CXCR4 signaling result in rapid mobilization.