Regulation of CD40 ligand expression in systemic lupus... : Current Opinion in Rheumatology (original) (raw)
Systemic lupus erythematosus and Sjögren syndrome
Department of Medicine, Hospital for Special Surgery and Weill Medical College of Cornell University, New York City, New York, USA.
Correspondence to Mary K. Crow, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA; e-mail: [email protected]
Abstract
Production of pathogenic autoantibodies in systemic lupus erythematosus (SLE) requires T cell help, along with ligation of the B cell surface immunoglobulin receptor by antigen. It is likely that macrophages, dendritic cells, and endothelial cells are also activated by interactions with T cells and contribute to lupus pathology. CD40 ligand (CD40L, CD154), a member of the tumor necrosis factor family of cell surface molecules, mediates these contact dependent signals delivered by CD4 + T helper cells to CD40 + target cells. Recent data from SLE patients and murine lupus models have demonstrated prolonged expression of CD40L on lupus T cells and its capacity to mediate excessive B cell activation. This review summarizes the current information regarding transcriptional and post-transcriptional regulation of CD40L expression in normal and SLE T cells. More complete characterization of the mechanisms that regulate the magnitude and duration of CD40L expression should suggest new approaches to modulate this promising therapeutic target.
© 2001 Lippincott Williams & Wilkins, Inc.