Tissue-resident specialized T cells promote the migration of local tissue dendritic cells: immune regulation at the local tissue level (CAM4P.155)

Abstract

Abstract Dendritic cells (DC) that primarily reside in tissues carry antigens to local lymphoid organs to induce immunity or tolerance. We posit that a defect in the migration of tissue-DCs may predispose to autoimmunity in a tissue-specific manner; and an improved migration of tissue-DC may ameliorate disease in the respective organ. Here, we demonstrate that treatment of lupus dermatitis-prone MRL-lpr and MRL+/+ mice that exhibit a profound defect in the migration of skin-DC with a glycolipid αGalCer reduced the severity of dermatitis and enhanced the migration of skin-DCs, more so in Langerhans cells (LC; p=0.004) than in Lang+dDC (p=0.03). This effect of αGalCer was independent of its effect on iNKT cells, but required the presence of CD1d. Furthermore, αGalCer treatment enhanced the numbers of epidermis-resident γδ T cells in MRL-lpr mice that had reduced numbers of γδ T cells as compared to MHC-matched control mice. Finally, gd T cell-deficient mice had reduced skin-DC migration, and isolated skin-gd T cells directly promoted the migration of LC via CD40L-CD40 interaction. These data elucidate a new mechanism of regulation of skin-DC homeostasis whereby skin-gd T cells normally facilitate LC migration from skin to cutaneous lymph node. Such ‘local’ control of migratory behavior of tissue-DC can regulate immune response in a tissue-specific manner. This mechanism of skin-DC homeostasis is disrupted in lupus dermatitis, but can be repaired by treatment with a glycolipid.