Autoantibody induction by DNA-containing immune complexes requires HMGB1 with TLR2/miR-155 pathway (P4040)

Abstract

Abstract Anti-dsDNA autoantibody has been reported as a central pathogenic factor of SLE. However, the mechanisms of anti-dsDNA antibody production still remain unclear. Recent evidence indicates that circulating DNA-containing immune complexes, one of the hallmarks of SLE, might be involved in the autoantibody production. Here we mainly explored the potential role and underlying mechanisms of DNA-containing immune complexes in the anti-dsDNA antibody production. We found that these immune complexes provoked anti-dsDNA antibody production primarily through their HMGB1 component, whose level was highly and positively correlated with the anti-dsDNA antibody level in SLE patients. Furthermore, the HMGB1-mediated autoantibody production was in a TLR2/MyD88 dependent pattern, and modulated by the miR-155 via targeting Ets-1. Our results firstly reported the crucial role of HMGB1 component of DNA-containing immune complexes in the autoantibody production, which was mediated and regulated by TLR2/MyD88/miR-155/Ets-1 pathways. These findings may provide novel mechanistic insight into the persistent anti-dsDNA antibody production and new clues for the development of therapeutic strategies for SLE.