Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models

Abstract

Systemic lupus erythematosus (SLE) is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys. The precise immunological events that trigger the onset of clinical manifestations of SLE are not yet well understood. However, research using various mouse strains of spontaneous and inducible lupus in the last two decades has provided insights into the role of the immune system in the pathogenesis of this disease. According to our present understanding, the immunological defects resulting in the development of SLE can be categorized into two phases: (a) systemic autoimmunity resulting in increased serum antinuclear and antiglomerular autoantibodies and (b) immunological events that occur within the target organ and result in end organ damage. Aberrations in the innate as well as adaptive arms of the immune system both play an important role in the genesis and progression of lupus. Here, we will review the present understanding--as garnered from studying mouse models--about the roles of various immune cells in lupus pathogenesis.

Figure 1

Pathogenic mechanisms of systemic lupus. Different subpopulations of immune cells interplay to directly or indirectly regulate other subpopulations by releasing different cytokines and other mediators of inflammation, thereby contributing to the progression of the systemic disease. The hyperactivated leukocytes as well as the pathogenic autoantibodies and immune complexes resulting from the systemic disease ultimately play an important role in local autoimmunity and end organ disease within target organs like the kidneys. Ab, antibody; BAFF, B-cell activation factor; DC, dendritic cell; IC, immune complex; IFN-I, interferon-I; IL-10, interleukin-10; MΦ, macrophage; MHC, major histocompatibility complex; self-Ag, self-antigen; TCR, T-cell receptor; TGF-β, transforming growth factor-beta.