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Publication : CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice.

First Author  Noda M Year  2011
Journal  Blood Volume  117
Issue  2 Pages  451-8
PubMed ID  20944068 Mgi Jnum  J:168425
Mgi Id  MGI:4888187 Doi  10.1182/blood-2010-04-277897
Citation  Noda M, et al. (2011) CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice. Blood 117(2):451-8
abstractText  Natural killer (NK) cells are granular lymphocytes that are generated from hematopoietic stem cells and play vital roles in the innate immune response against tumors and viral infection. Generation of NK cells is known to require several cytokines, including interleukin-15 (IL-15) and Fms-like tyrosine kinase 3 ligand, but not IL-2 or IL-7. Here we investigated the in vivo role of CXC chemokine ligand-12 (CXCL12) and its primary receptor CXCR4 in NK-cell development. The numbers of NK cells appeared normal in embryos lacking CXCL12 or CXCR4; however, the numbers of functional NK cells were severely reduced in the bone marrow, spleen, and peripheral blood from adult CXCR4 conditionally deficient mice compared with control animals, probably resulting from cell-intrinsic CXCR4 deficiency. In culture, CXCL12 enhanced the generation of NK cells from lymphoid-primed multipotent progenitors and immature NK cells. In the bone marrow, expression of IL-15 mRNA was considerably higher in CXCL12-abundant reticular (CAR) cells than in other marrow cells, and most NK cells were in contact with the processes of CAR cells. Thus, CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adults, and CAR cells might function as a niche for NK cells in bone marrow.
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