LIIPAT, Institute of Pathology and Centre for Immune Regulation, Oslo University Hospital and University of Oslo, Norway.
Br J Dermatol. 2011 Oct;165(4):792-801. doi: 10.1111/j.1365-2133.2011.10430.x.
Interferon (IFN)-α-producing plasmacytoid dendritic cells (pDCs), inflammatory CD11c+CD1c- myeloid dendritic cells (mDCs) and macrophages have been found to contribute to the pathogenesis of psoriasis. Heliotherapy is a well-established treatment modality of this disease, although the details of how the effects are mediated are unknown.
To test the hypothesis that exposure to natural sun affects pathogenic DC subsets in lesional skin.
Skin biopsies were obtained from lesional and nonlesional skin in 10 patients with moderate to severe psoriasis subjected to controlled sun exposure on Gran Canaria. Biopsies were obtained at baseline, day 2 and day 16 and examined by immunohistochemistry.
Sixteen days of heliotherapy had excellent clinical effect on patients with psoriasis, with significant reductions in Psoriasis Area and Severity Index (PASI) scores. In lesional skin pDC numbers and expression of MxA, a surrogate marker for IFN-α, were rapidly reduced. Inflammatory CD11c+CD1c- mDCs were significantly reduced whereas resident dermal CD11c+CD1c+ mDCs were unaffected. Expression levels of the maturation marker DC-LAMP (CD208) on mDCs were significantly reduced after sun exposure, as were the numbers of lesional dermal macrophages. A decrease of dermal DC subsets and macrophages was already observed after 1 day of sun exposure. An additional finding was that DC-SIGN (CD209) is primarily expressed on CD163+ macrophages and not DCs.
The clinical improvement in psoriasis following sun exposure is associated with rapid changes in dermal DC populations and macrophages in lesional skin, preceding the clinical effect. These findings support the concept that these DC subsets are involved in the pathogenesis of psoriasis and suggest that sun-induced clinical benefit may partly be explained by its effect on dermal DCs.
干扰素（IFN）-α 产生的浆细胞样树突状细胞（pDC）、炎症性 CD11c+CD1c- 髓样树突状细胞（mDC）和巨噬细胞已被发现有助于银屑病的发病机制。光疗是治疗这种疾病的一种成熟方法，尽管其作用机制尚不清楚。
检验假设，即暴露于自然阳光下会影响病变皮肤中的致病性 DC 亚群。
对 10 名中度至重度银屑病患者进行对照性日光暴露治疗，在病变和非病变皮肤中采集活检标本。在基线、第 2 天和第 16 天采集活检标本，并进行免疫组织化学检查。
16 天的光疗对银屑病患者有极好的临床疗效，银屑病面积和严重程度指数（PASI）评分显著降低。在病变皮肤中，pDC 数量和 IFN-α 的替代标志物 MxA 的表达迅速减少。炎症性 CD11c+CD1c- mDC 明显减少，而驻留真皮 CD11c+CD1c+ mDC 不受影响。mDC 上的成熟标志物 DC-LAMP（CD208）的表达水平在暴露于阳光下后显著降低，病变真皮巨噬细胞的数量也减少。在暴露于阳光 1 天后，真皮 DC 亚群和巨噬细胞的数量已经减少。另一个发现是，DC-SIGN（CD209）主要表达在 CD163+巨噬细胞上，而不是 DC 上。
暴露于阳光下后银屑病的临床改善与病变皮肤中真皮 DC 群体和巨噬细胞的快速变化有关，早于临床疗效。这些发现支持了这些 DC 亚群参与银屑病发病机制的概念，并表明阳光诱导的临床益处可能部分解释为其对真皮 DC 的影响。
