Cadherins and Langerhans cell immunobiology.

Langerhans cells represent the epidermal contingent of a family of potent accessory cells termed 'dendritic cells'. Langerhans cells (and perhaps related cells in the dermis) are thought to be required for immune responses directed against foreign antigens and neoantigens that are encountered in skin. The 'life cycle' of the Langerhans cell is characterized by at least two distinct stages. Langerhans cells in epidermis (the 'sentinels') can ingest particulates and process antigens efficiently, but are weak stimulators of unprimed T cells. In contrast, Langerhans cells that have been induced to migrate to lymph nodes after contact with antigen in epidermis (the 'messengers') are not phagocytic and have limited antigen-processing capabilities, but are potent stimulators of naïve T cells. If Langerhans cells are to fulfil both their 'sentinel' and 'messenger' roles, they must be able to persist in epidermis for considerable periods, and also be able to exit epidermis in a controlled fashion after exposure to antigen. Thus, regulation of Langerhans cell-keratinocyte adhesion represents a key control point in Langerhans cell trafficking and function. Langerhans cells express E-cadherin, a homophilic adhesion molecule that is prominently represented in epithelia. Keratinocytes also express this adhesion molecule, and E-cadherin clearly mediates adhesion of murine Langerhans cells to keratinocytes in vitro. We presume that E-cadherin is involved in the localization of Langerhans cells in epidermis. Murine thymocytes also express E-cadherin early in the course of their development, and it is likely that E-cadherin plays an as yet uncharacterized role in thymocyte-thymic epithelial cell adhesion and in T-cell development. Recently, it has also been demonstrated that some cutaneous T-cell lymphoma cell lines are E-cadherin+, so E-cadherin may also mediate clinically important leucocyte-epithelial interactions in disease states.