The IL-12-STAT4 axis in the pathogenesis of human systemic lupus erythematosus.

Generation of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). As demonstrated in a number of lupus mouse models, recent evidence suggests that both GC and extrafollicular pathways contribute to the generation of autoantibodies also in human SLE, and that CD11c IgD CD27 (double negative:DN) B cells play a central role in the latter pathway. In this mini-review, the author will first briefly summarize the features of CD11c DN B cells in human SLE, and discuss how the IL-12-STAT4 axis might contribute to the generation of autoantibodies in SLE. In addition, various types of CD4 helper T cell subsets promoting the generation of autoantibodies in SLE will be described, and finally it will be discussed how these recent discoveries contribute to understanding of SLE pathogenesis and treatment of SLE patients.