CXCR4 engagement promotes dendritic cell survival and maturation.
It has been reported that human monocyte derived-dendritic cells (DCs) express CXCR4, responsible for chemotaxis to CXCL12. However, it remains unknown whether CXCR4 is involved in other functions of DCs. Initially, we found that CXCR4 was expressed on bone marrow-derived DCs (BMDCs). The addition of specific CXCR4 antagonist, 4-F-Benzoyl-TN14003, to the culture of mouse BMDCs decreased their number, especially the mature subset of them. The similar effect was found on the number of Langerhans cells (LCs) but not keratinocytes among epidermal cell suspensions. Since LCs are incapable of proliferating in vitro, these results indicate that CXCR4 engagement is important for not only maturation but also survival of DCs. Consistently, the dinitrobenzene sulfonic acid-induced, antigen-specific in vitro proliferation of previously sensitized lymph node cells was enhanced by CXCL12, and suppressed by CXCR4 antagonist. These findings suggest that CXCL12-CXCR4 engagement enhances DC maturation and survival to initiate acquired immune response.
Kabashima
Kenji
K
Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Sugita
Kazunari
K
Shiraishi
Noriko
N
Tamamura
Hirokazu
H
Fujii
Nobutaka
N
Tokura
Yoshiki
Y
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000276:immunology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
C477728:4-fluorobenzoyl-TN-14003; C514936:CXCR4 protein, mouse; D006241:Haptens; D010455:Peptides; D019718:Receptors, CXCR4