Effect of CXCR4 on leukocyte trafficking. In bone marrow, CXCR4 is expressed on pDCs and preDCs, the latter developing into DC1 and DC2 in peripheral tissues. CXCR4 gain of function in WHIM syndrome, and in Cxcr4+/1013 mice, enhances the interaction of this receptor with its ligand, CXCL12, thereby increasing bone marrow cellularity of multiple leukocyte types, including pDCs and preDCs, and decreasing numbers of these cells in the blood. In the skin, either blockade of CXCR4, or its overactivity, has the same effect of reducing skin DC migration to regional LNs. The CXCR4 inhibitor, AMD3100, reduces skin DC migration in wild-type mice but does not reverse the gain-of-function–dependent reduction in skin DC migration to regional LNs seen in Cxcr4+/1013 mice. Figure generated by Jennifer Martinez, National Institute of Environmental Health Sciences, using Biorender.

Effect of CXCR4 on leukocyte trafficking. In bone marrow, CXCR4 is expressed on pDCs and preDCs, the latter developing into DC1 and DC2 in peripheral tissues. CXCR4 gain of function in WHIM syndrome, and in Cxcr4+/1013 mice, enhances the interaction of this receptor with its ligand, CXCL12, thereby increasing bone marrow cellularity of multiple leukocyte types, including pDCs and preDCs, and decreasing numbers of these cells in the blood. In the skin, either blockade of CXCR4, or its overactivity, has the same effect of reducing skin DC migration to regional LNs. The CXCR4 inhibitor, AMD3100, reduces skin DC migration in wild-type mice but does not reverse the gain-of-function–dependent reduction in skin DC migration to regional LNs seen in Cxcr4+/1013 mice. Figure generated by Jennifer Martinez, National Institute of Environmental Health Sciences, using Biorender.

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