Figure 3.

A model for recognition of self-DNA and self-RNA by pDCs. LL37 binds self-DNA and self-RNA fragments released by dying cells to form aggregated and condensed structures that are protected from extracellular nuclease degradation. HMGB1, derived from the dying cells, binds aggregated self-DNA-LL37 complexes or dsDNA-autoantibodies immune complexes and promotes their association with TLR9 through interacting with RAGE. In SLE, the aberrantly expressed IFN-α from pDCs, together with IL-6, stimulates the differentiation of autoreactive B cells into plasma cells and expression of B cell survival factor BAFF. This could contribute to amplification of the pathogenic loop in which pDCs produce more type I IFNs and subsequently promote the differentiation of autoreactive plasma cells that would further secret autoantibodies to form immune complexes to activate pDCs.