The role of dead cell clearance in the etiology and pathogenesis of systemic lupus erythematosus: dendritic cells as potential targets

Abstract

Overwhelming apoptosis combined with a deficiency in clearing apoptotic cells is thought to be an important etiopathogenic event in the autoimmune disease systemic lupus erythematosus (SLE). Lazy macrophages, complement or DNase I deficiency as well as insufficient natural IgM might be important factors leading to such a clearance deficiency. A defective clearance of apoptotic cells leads to the activation and maturation of plasmacytoid and myeloid dendritic cells (DCs) by material derived from secondary necrotic cells carrying modified autoantigens. This results in the presentation of autoantigens to autoreactive T and B cells in an immunogenic manner, thereby leading to autoantibody production, chronic inflammation and severe tissue damage. Since DC activation and IFN-α production by plasmacytoid dendritic cells play a critical role in the course of SLE pathogenesis, therapeutic intervention to end this vicious cycle might be a promising approach for treating the disease.

Keywords: IFN signature; NETosis; apoptosis; autoimmunity; clearance deficiency; dendritic cells; secondary necrosis; systemic lupus erythematosus; tolerance; toll-like receptor.