Dendritic cells (DCs) initiate and control the adaptive immune response against infections. However, their contributions to the anti-self adaptive immune response in autoimmune disorders like systemic lupus erythematosus are uncertain. By constitutively deleting DCs in MRL.Faslpr mice, we show that they have complex roles in murine lupus. The net effect of DC deletion was to ameliorate disease. DCs were crucial for the expansion and differentiation of T cells but, surprisingly, not required for their initial activation. Correspondingly, kidney interstitial infiltrates developed in the absence of DCs, but failed to progress. DC deletion concomitantly decreased inflammatory and regulatory T cell numbers. Unexpectedly, plasmablast numbers and autoantibody concentrations depended on DCs, in contrast to total serum immunoglobulin concentrations, suggesting an effect of DCs on extrafollicular humoral responses. These findings reveal that DCs operate in unanticipated ways in murine lupus and validate them as a potential therapeutic target in autoimmunity.
Bibliographical noteFunding Information:
We thank J. Martinez-Barbera for the generous gift of the Rosa26-eGFP-DTA mice. We thank Yale Animal Resources Center for outstanding animal husbandry. Supported by National Institutes of Health grant R01-AR044077 (M.J.S.), Deutsche Forschungsgemeinschaft (fellowship to L.L.T.), and the Lupus Research Institute and the Yale Skin Diseases Research Center (D.H.K.).