Altered cell–cell and cell–matrix interactions in the development of systemic autoimmunity

Abstract

MΦ of mice from the major inbred models of systemic lupus erythematosus (SLE) have an identical defect affecting the activity of the cytoskeletal regulator and G-protein Rho. This abnormality is triggered by apo cells. Strikingly, SLE-prone MΦ show normal Rho activity when cultured in the absence of apo cells. We used gene arrays to identify adhesion-related gene products that are abnormally expressed by MΦ from prediseased 4–6-week-old SLE-prone MRL mice in the presence of serum lipids mimicking apo cells (SL-Apo). MΦ of MRL mice differentially expressed 42 adhesion-related genes in the presence of SL-Apo. Of these, 32 were expressed normally in the absence of SL-Apo. As adhesive interactions play a major role in lymphocyte activation, the detected apo cell-dependent abnormality could predispose to the development of autoimmunity. Indeed, several recent genetic studies support a role for adhesion-related genes in the pathogenesis of chronic autoimmunity.

• Cytoskeleton
• SLE
• rodent
• autoimmunity
• gene array