Wang B, Fujisawa H, Zhuang L, Kondo S, Shivji G M, Kim C S, Mak T W, Sauder D N
Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, ON, Canada.
J Immunol. 1997 Dec 15;159(12):6148-55.
Epidermal Langerhans cells (LC) belong to the dendritic cell family and represent the major APC within the skin. LC capture epicutaneous Ag, migrate into regional lymph nodes, and present Ag to T cells, thereby initiating primary immune response. The migratory properties of LC are an essential component of their function. The molecular mechanisms responsible for LC migration are far less defined. However, evidence has been accumulating to suggest that TNF-alpha, a major proinflammatory cytokine, plays an important role in promoting DC migration. To confirm the role of TNF-alpha in LC migration and to examine which type of TNF receptor signaling is involved in such an event, we utilized gene-targeted knockout mice lacking TNF receptor p55 or p75. The migration of LC was assessed by examining the frequency of hapten-bearing cells in draining lymph nodes following hapten FITC painting, and the accumulation of dendritic cells in draining lymph nodes after intradermal injection of TNF-alpha. While LC migration was normal in p55-deficient mice, the migration was markedly depressed in p75-deficient mice. Receptor p75-deficient mice also demonstrated a hyporesponsiveness in allergen-induced contact dermatitis, but a normal responsiveness in irritant-induced contact dermatitis. These results suggest that p75-dependent signaling plays a crucial role in the migration of LC and in the initiation of cutaneous immune responses.
表皮朗格汉斯细胞（LC）属于树突状细胞家族，是皮肤内主要的抗原呈递细胞（APC）。LC捕获经皮抗原，迁移至局部淋巴结，并将抗原呈递给T细胞，从而启动初次免疫反应。LC的迁移特性是其功能的重要组成部分。负责LC迁移的分子机制仍不太明确。然而，越来越多的证据表明，主要促炎细胞因子肿瘤坏死因子-α（TNF-α）在促进树突状细胞迁移中起重要作用。为了证实TNF-α在LC迁移中的作用，并研究何种类型的TNF受体信号传导参与此过程，我们利用了缺乏TNF受体p55或p75的基因靶向敲除小鼠。通过检测经荧光素异硫氰酸酯（FITC）致敏后引流淋巴结中携带半抗原细胞的频率，以及皮内注射TNF-α后引流淋巴结中树突状细胞的积聚情况，来评估LC的迁移。虽然p55缺陷小鼠中LC迁移正常，但p75缺陷小鼠中迁移明显受抑。p75受体缺陷小鼠在变应原诱导的接触性皮炎中也表现出反应低下，但在刺激物诱导的接触性皮炎中反应正常。这些结果表明，p75依赖性信号传导在LC迁移及皮肤免疫反应的启动中起关键作用。
