Pathomechanisms of lichen planus autoimmunity elicited by cross-reactive T cells.
Lichen planus (LP) is an idiopathic inflammatory disease of the skin and mucous membranes, characterized by an autoimmune attack on the epidermis by skin-infiltrating T cells. It remains unknown, however, how such autoaggressive T cells could be activated in vivo to cause epidermal damage; we hypothesize that memory T cells specific for a previously encountered virus could cross-react with other antigens, including contact allergens, drugs and other heterologous viruses in the absence of cognate antigen, and cause epidermal damage. This hypothesis provides an explanation for an intimate relationship between exposure to a number of exogenous agents, such as viruses and drugs, and the development of LP. In addition to T cells migrating from the circulation, T cells indigenously residing in the epidermis, such as intraepidermal CD8+ T cells, would also be involved in tissue damage. This population is typically detected at high frequencies in the resting lesion of fixed drug eruption, which is a simplified disease model for LP. Fucosyltransferase VII, essential for generating E-selectin ligand, is shown to play an indispensable role in inducing the accumulation of relevant skin-homing T cells at sites of LP lesions; however, the alternative notion should be appreciated that T cell recruitment to the skin is also crucial for host defense and that T cells frequently found in LP lesions could display beneficial properties for the host.
Shiohara
Tetsuo
T
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan. tpshio@kyorin-u.ac.jp
Mizukawa
Yoshiko
Y
Takahashi
Ryo
R
Kano
Yoko
Y
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000276:immunology; D005647:Fucosyltransferases / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008010:Lichen Planus / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D009092:Mucous Membrane / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology
D001324:Autoantigens; D019040:E-Selectin; D005647:Fucosyltransferases