Dendritic cells (DCs) have previously been implicated in the pathogenesis of the autoimmune disease lupus. Blimp-1, a known regulator of B cells and T cells, is now shown to also regulate the immune tolerance function of DCs, providing new insights into the role of these key immune cells in lupus (J. Exp. Med. 208, 2193–2199).

A polymorphism in Blimp-1 was previously identified as risk variant for systemic lupus erythematosus (SLE), indicating that this factor might be important in SLE pathogenesis. By investigating mice in which Blimp-1 had been selectively knocked out in DCs, Sun Jung Kim et al. showed that Blimp-1 expression in DCs is required for immune tolerance in female mice, but not in males. DCs lacking Blimp-1 from female mice showed increased production of the proinflammatory cytokine interleukin-6, promoted the induction of follicular T helper cells and enhanced germinal center responses. These mice also developed autoreactive antibodies that carried multiple mutations, consistent with a germinal center response.

Together, these gender-dependent responses to Blimp-1 knockout in DCs are reminiscent of the human lupus phenotype. It will therefore be interesting to investigate how the Blimp-1 polymorphism identified in genome-wide association studies influences Blimp-1 expression and DC function in human studies.