The direct action of 1alpha,25(OH)2-vitamin D3 on purified mouse Langerhans cells.
The action of vitamin D(3) on Langerhans cells (LCs) is not well understood. Using highly purified murine LCs (>95%), we investigated the direct action of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on their functions. 1,25(OH)(2)D(3) inhibited the expression of cell surface molecules including I-A(d), CD40, CD80, and CD86, leading to impaired ability of LCs to stimulate allogenic T cells in the mixed leukocyte reaction. Furthermore, this reagent inhibited chemotaxis of LCs to CCL21 and their survival. Interestingly, 1,25(OH)(2)D(3) reduced the IL-10 production by LCs, whereas the production of IL-6 and IL-12p40 upon activation by CD40 ligation was enhanced. With regard to inflammatory cytokines and chemokines, 1,25(OH)(2)D(3) upregulated the production of IL-1beta, CCL3, CCL4, and CCL5. The production of Th2-type chemokines, represented by CL17 and CCL22, was inhibited, whereas IFN-gamma-triggered production of Th1-type chemokines, represented by CXCL9, CXCL10, and CXCL11, was augmented. These data indicate that the mode of regulation of cytokine and chemokine production in association with 1,25(OH)(2)D(3) treatment seems to be another characteristic discriminating LCs from classical myeloid dendritic cells.
Fujita
Hideki
H
Department of Dermatology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. hfuji-tky@umin.ac.jp
Asahina
Akihiko
A
Komine
Mayumi
M
Tamaki
Kunihiko
K
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054422:Chemokine CCL22; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000943:Antigens, Differentiation; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D016753:Interleukin-10; D002117:Calcitriol