Evidence that vitamin D(3) promotes mast cell-dependent reduction of chronic UVB-induced skin pathology in mice.
Mast cell production of interleukin-10 (IL-10) can limit the skin pathology induced by chronic low-dose ultraviolet (UV)-B irradiation. Although the mechanism that promotes mast cell IL-10 production in this setting is unknown, exposure of the skin to UVB irradiation induces increased production of the immune modifying agent 1alpha,25-dihydroxyvitamin D(3) (1alpha,25[OH](2)D(3)). We now show that 1alpha,25(OH)(2)D(3) can up-regulate IL-10 mRNA expression and induce IL-10 secretion in mouse mast cells in vitro. To investigate the roles of 1alpha,25(OH)(2)D(3) and mast cell vitamin D receptor (VDR) expression in chronically UVB-irradiated skin in vivo, we engrafted the skin of genetically mast cell-deficient WBB6F(1)-Kit(W/W-v) mice with bone marrow-derived cultured mast cells derived from C57BL/6 wild-type or VDR(-/-) mice. Optimal mast cell-dependent suppression of the inflammation, local production of proinflammatory cytokines, epidermal hyperplasia, and epidermal ulceration associated with chronic UVB irradiation of the skin in Kit(W/W-v) mice required expression of VDR by the adoptively transferred mast cells. Our findings suggest that 1alpha,25(OH)(2)D(3)/VDR-dependent induction of IL-10 production by cutaneous mast cells can contribute to the mast cell's ability to suppress inflammation and skin pathology at sites of chronic UVB irradiation.
Biggs
Lisa
L
Division of Human Immunology, Centre for Cancer Biology, South Australia, Australia.
Yu
Chunping
C
Fedoric
Boris
B
Lopez
Angel F
AF
Galli
Stephen J
SJ
Grimbaldeston
Michele A
MA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002117:Calcitriol / Q000096:biosynthesis / Q000528:radiation effects; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000627:therapeutic use*; D016207:Cytokines / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D016753:Interleukin-10 / Q000096:biosynthesis / Q000528:radiation effects; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010858:Pigmentation / Q000528:radiation effects; D011859:Radiography; D018167:Receptors, Calcitriol / Q000172:deficiency / Q000235:genetics; D012867:Skin / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology / Q000473:pathology* / Q000528:radiation effects; D016038:Skin Transplantation; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016207:Cytokines; D018167:Receptors, Calcitriol; D016753:Interleukin-10; D002762:Cholecalciferol; D002117:Calcitriol