Mechanisms Of Dc Migration

When peripheral tissues such as the skin are inflamed, infiltrated by microbes, or triggered by haptens, resident DCs start to emigrate via the afferent lymphatics to reach the draining lymph node (Fig. 2). This has been demonstrated by the transport of haptenized FITC, applied through skin painting, which was then transported by the skin DC populations (7).

After activation, epidermal LCs start to downregulate E-cadherin, the anchor receptor for binding to keratinocytes (11,12), and also a6-integrins, which enable the binding to the basement membrane (13) but upregulate CD44 (14). To cut a hole into the basement membrane to allow LC passage, the expression of the matrix metalloproteinases MMP2 and MMP9 is then required next (15). Endogenously released proinflammatory cytokines such as TNF-a or IL-1^, but also osteopontin, are major factors to promote the motility of DCs and thereby the migration process (16-19). Similarly, injections of LPS mobilized splenic DCs to migrate into the T-cell areas of the white pulp (20,21). Both endogenous and exogenous types of stimulators then induce other effector molecules, such as IL-16 (22), the multi drug resistance pump MDR-1, and chemokines (23), which further

Figure 2 Molecular processes involved in Langerhans cell emigration from the skin. Inflammaory or pathogen-induced maturation induces a cascade of events which enable the cells to leave the epidermis and find their way through the lymphatics and finally to the draining lymph node.

promote LC emigration from the skin. Simultaneously, the chemokine receptor CCR7 is induced to guide the LCs through the afferent lymphatics that express the ELC/CCL19 and SLC/CCL21-leu chemokine and into the lymph node by the ELC/CCL19 and SLC/CCL21-ser chemokines (24-27).

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