Does deleting dendritic cells delete autoimmunity?

Abstract

A role for DCs in autoimmunity remains to be fully delineated. In this issue of Immunity, Teichmann et al. reveal critical functions for DCs in augmenting, but surprisingly not in initiating, spontaneous autoimmune disease.

Figure 1. A model for the role of dendritic cells in autoimmunity

When DCs are replete (left), DCs present self-antigen to auto-reactive T cells, which proliferate, differentiate and acquire effector functions such as IFNγ production. Activated CD4⁺ T cells also undergo cognate interactions with antigen-specific B cells, forming germinal centers (not shown) and antibody-secreting, long-lived plasma cells. In addition, a major source of auto-antibodies in lupus, short-lived plasmablasts, are derived from extrafollicular responses which may involve direct DC-B cell interactions. In contrast, when DCs are absent (right), other as yet undefined APCs initiate the activation of auto-reactive CD4⁺ T cells that are in turn able to drive the humoral response. However, full expansion of T and B cells fails in DC-deficient animals. Finally, plasmablast numbers are reduced or absent, possibly due to the absence of direct DC-B cell interactions or cytokine support provided by plasmacytoid DCs, thus lowering auto-antibody titers. The net effect of reduced T and B cell activation, auto-antibodies, and inflammatory cytokines in the absence of DCs is reduced development of experimental systemic lupus erythematosus (SLE).