| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
The effect of type I IFNs on myeloid dendritic cells(DCs) is to promote their maturation. To test if this is also the case with Langerhans cells(LCs), we isolated LCs at high purity from BALB/c mouse skin by using the panning method. Surprisingly, type I IFNs inhibited the expression of costimulatory molecules with impaired ability of LCs to stimulate the proliferation of co-cultured T cells and reduced migratory activity to CCL21. In addition, type I IFNs inhibited LC IL-6and IL-12p40 production dose dependently. The mode of regulation of other cytokines and chemokines in LCs was complex and different from that in splenic DCs. We then performed punch bipsies from the perilesional skin, lesional skin, and distant uninvolved skin of patients with psoriasis vulgaris, the pathogenesis of which may be associated with local production of type I IFNs. LCs were increased in number and activated in the epidermis, as well as dermal DCs in the epidermal-dermal junction of perilesional skin. In addition, we found only a few BDCA2+ plasmacytoid DCs that are known to be the source of type I IFNs in the skin. Finally, we examined the responsiveness of mouse LCs to vitamin D, because topical vitamin D application is effective in the treatment of psoriasis. The mode of regulation of LC function by vitamin D was similar to that by type I IFNs in many aspects. Curiously, however, vitamin D stimulated IL-6 and IL-12p40 production of purified LCs, while suppressing that of IL-10. These results do not support the concept that typeI IFNs may be involved in the pathogenesis of psoriasis, nor do they support the fact that vitamin D is effective in its treatment. Dermal DCs, but not LCs, may play a more important role in the pathogenesis of psoriasis.
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