Theme Clarification of the molecular and cellular mechanisms of central and peripheral tolerance to pemphigus antigens Pemphigus is a severe autoimmune bullous dermatosis caused by IgG autoantibodies against desmogleins. In a murine pemphigus model established by us, we were able to clarify the B and T cell aspects of the disease subsequent to the loss of immunological tolerance. In this project, we attempt to clarify how immunological tolerance to desmogleins is established under normal conditions, and also the processes leading to its disruption. Special focus will be placed on events in the thymus as well as on the dendritic cells in the skin. Development of treatment for scarring alopecia using bioengineered human hair follicles The goal of the present project is to bioengineer human hair follicles with maintenance of their full function and structure, for potential use in the treatment of permanent hair loss. We shall attempt to regenerate human hair follicles using a cell mixture of hair follicle bulge stem cells and dermal papilla cells with optimized hair-inductive capacity. The hair reorganization potency of the cell mixture will be assessed by hair reconstitution assays in vivo or using a 3-D culture system.