Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells.
Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells.
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DOI：
10.1038/jid.2008.194
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发表时间：
2009-01
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髓样真皮树突状细胞(DC)聚集在银屑病等慢性炎症组织中。这些细胞在银屑病发病机制中的重要性是通过比较T细胞和DC细胞计数来提示的，DC的数量超过T细胞。我们之前已经发现CD11c+BDCA-1+细胞是在正常皮肤中发现的主要驻留真皮DC群体。我们现在发现银屑病皮损皮肤有两类真皮DC：1)CD11c+BDCA-1+细胞，表型与正常皮肤相似；2)CD11c+BDCA-1−细胞，表型不成熟，产生炎性细胞因子。与正常皮肤相比，银屑病皮损中BDCA-1+DC的数量没有增加，而BDCA-1−树突状细胞的数量增加了30倍。为了进行功能研究，我们对银屑病患者皮肤单个细胞悬液进行了FACS分选，以分离这两个皮肤DC群体，并将它们培养为异基因MLR中的刺激物。BDCA-1+和BDCA-1−髓系真皮DC均可诱导T细胞增殖，并分化为Th1和Th17细胞。此外，银屑病患者皮肤树突状细胞诱导了一群同时产生IL-17和干扰素-γ的活化T细胞，这是正常皮肤树突状细胞所不能诱导的。由于银屑病被认为是一种混合的Th17/Th1疾病，因此这些IL-17+干扰素γ+细胞的诱导可能是致病的。这些细胞因子、产生细胞因子的T细胞以及诱导炎性树突状细胞可能都是治疗银屑病的重要新靶点。
Myeloid dermal dendritic cells (DCs) accumulate in chronically inflamed tissues such as psoriasis. The importance of these cells for psoriasis pathogenesis is suggested by comparative T cell and DC cell counts, where DCs outnumber T cells. We have previously identified CD11c+BDCA-1+ cells as the main resident dermal DC population found in normal skin. We now show that psoriatic lesional skin has two populations of dermal DCs: 1) CD11c+BDCA-1+ cells which are phenotypically similar to those contained in normal skin, and 2) CD11c+BDCA-1− cells which are phenotypically immature and produce inflammatory cytokines. While BDCA-1+ DCs are not increased in number in psoriatic lesional skin compared to normal skin, BDCA-1− DCs are increased 30-fold. For functional studies, we FACS-sorted psoriatic dermal single cell suspensions to isolate these two cutaneous DC populations, and cultured them as stimulators in an allo-MLR. Both BDCA-1+ and BDCA-1− myeloid dermal DC populations induced T cell proliferation, and polarized T cells to become Th1 and Th17 cells. In addition, psoriatic dermal DCs induced a population of activated T cells that simultaneously produced IL-17 and IFN-γ, which was not induced by normal skin dermal DCs. As psoriasis is believed to be a mixed Th17/Th1 disease, it is possible that induction of these IL-17+IFNγ+ cells is pathogenic. These cytokines, the T cells that produce them, and the inducing inflammatory DCs may all be important new therapeutic targets in psoriasis.
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