CXCL12-CXCR4 Engagement Is Required for Migration of Cutaneous Dendritic Cells

Abstract

CCR7 is regarded as an essential chemokine receptor for cutaneous dendritic cell (DC) migration into the regional lymph nodes. However, complete migratory inhibition cannot be obtained in CCR7-deficient mice, suggesting that there exist other chemokine receptors involved in this process. Initially, we found that CXCR4 was highly expressed on migrated cutaneous DCs and that its ligand, CXCL12, was detected in the LYVE-1 ؉ lymphatic vessels in the skin. FITC-induced cutaneous DC migration into the draining lymph nodes was impaired by the specific CXCR4 antagonist 4-F-Benzoyl-TN14003. Among FITC ؉ cells, Langerin

Visualizing dendritic cell migration within the skin

“…In addition, while CCR7 appears to be required for DC migration to LNs, additional chemokine receptors may further facilitate this process, particularly in inXammatory conditions. Indeed such a role has been described for CXCR4/CXCL12 (Kabashima et al 2007). …”

Interaction of tumor cells and lymphatic vessels in cancer progression

“…The lymphatic vessel endothelium may express CXCL12 (stromal-derived factor 1) and CCL21 chemokines, which when bound to CXCR4 or CCR7 receptors on malignant cells lead to chemoattraction. 96,97 This chemoattraction mechanism is used in leukocyte homing. Thus, cancer cells, when expressing receptors for lymphatic-derived factors, may use such chemokine gradients to sense direction in the tumor microenvironment.…”

CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers

“…36 Other studies explored the activity of these agents in acute 76,77 and chronic leukemias, 54 multiple myeloma, 78 small cell lung cancer (SCLC), 50 malignant melanoma 74 and pancreatic cancer. 79 Besides these disease-oriented studies, T140 and its analogs have been used in basic studies exploring the function of CXCR4 in dendritic cell development 80 and migration, 81 B-cell homing and germinal center positioning within lymphatic tissues, 82 and HSC homing. 83 Currently, the T140 analog TN14003 is under clinical development by Biokine Therapeutics Ltd, Rehovot, Israel.…”