[Pathogenesis of systemic lupus erythematosus (LES)]

The refinement of our knowledge of the functioning of the immune system, both innate and adaptive, in the last decade has fundamentally modified the interpretation of the pathogenesis of systemic lupus erythematosus (SLE). In this autoimmune disease the main pathogenetic mechanism leads to the production of autoantibodies specific to self antigens (tolerated or not) favored by a genetic condition and triggered by endogenous factors, such as estrogens or exposure to sunlight, and exogenous factors, such as viruses. T cells were thought to play a predominant role. The identification of a population of B cells located in marginal areas of the germinal centers and equipped with receptors belonging to the family of Toll-like receptors (TLR) (either extracellular, such as TLR4, or intracellular, such as TLR3, which recognize DNA and RNA) and High Mobility Box Protein 1 (HMBP1), capable in a T-independent manner of self-reactive activities with IgG autoantibody production and release, has greatly advanced the understanding of the pathogenesis of SLE. The T and B lymphocyte populations interact in complex ways, with interference of tolerance-inducing regulatory T cells and inflammation-inducing Th17 cells, finely regulating the cross-talk in the lymphocyte system. This review will discuss the latest knowledge on the pathogenesis of SLE.