Current Knowledge of the Molecular Pathogenesis of Cutaneous Lupus Erythematosus.

Abstract

Cutaneous lupus erythematosus (CLE) is an autoimmune disease, which can be limited to the skin or associated with systemic lupus erythematosus (SLE). Gene expression analysis has revealed that both the innate and adaptive immune pathways are activated in CLE. Ultraviolet (UV) light, the predominant environmental factor associated with CLE, induces apoptosis in keratinocytes, and the endogenous nucleic acids released from the apoptotic cells are recognized via pattern recognition receptors, including Toll-like receptors. This leads to the production of type I interferon, a major contributor to the pathogenesis of CLE, by plasmacytoid dendritic cells. UV irradiation can also induce the externalization of autoantigens, such as SS-A/Ro, exposing them to circulating autoantibodies. T-helper 1 cells have been reported to play important roles in the adaptive immune response to CLE. Other environmental factors associated with CLE include drugs and cigarette smoke. Genetic factors also confer a predisposition to the development of CLE, and many susceptibility genes have been identified. Monogenetic forms of CLE also exist. This article aims to review current knowledge about the pathogenesis of CLE. A better understanding of the environmental, genetic, and immunoregulatory factors that drive CLE may provide important insights for the treatment of CLE.