Die Rolle der Gewebe-Mikroumgebung bei der Kontaktallergie

Allergic contact dermatitis (ACD) is a T cell-mediated inflammatory skin disease. In order to activate the T cell response, the innate immune system has to generate an inflammation that activates skin cells and triggers allergen-loaded dendritic cells (DC) to migrate to the local lymph nodes. There, DC confer the information about their tissue of origin and the site of antigen encounter to T cells which are induced to upregulate skin-specific homing receptors. This enables the recruitment of allergen-specific effector T cells to the skin following allergen contact. Similar findings were made for the small intestine. Our recent studies in the mouse model show a crucial role for the tissue microenvironment both for the inflammatory response and for the transfer of the topographical information from the DC to the T cells. Thus, we have found that Toll-like receptors and the IL-12/IL-12R system are important for DC activation by contact allergens and imply a role for endogenous TLR ligands generated during ACD. Moreover, cells of the peripheral tissue microenvironment provide information via soluble factors and cell-cell contact which license DC emigrating from skin but also DC emigrating from the small intestine to confer topographical information to T cells by imprinting tissue-specific homing receptors on the T cells in the draining lymph nodes. Our results illustrate the crucial role of the tissue context and of the communication between tissue-specific cell types for the shaping of immune responses. These findings underline the necessity to take into account the unique tissue microenvironments upon analysis of immune responses.