The association of complement protein C1q with apoptotic cells ingested by human dendritic cells modulates dendritic cell-mediated T cell activation (INC5P.332)

Abstract Humans deficient in complement protein C1q develop systemic lupus erythematosus (SLE) with nearly 100% penetrance, but the molecular mechanisms underlying this association have not yet been uncovered. Our previous studies have shown that human monocyte-derived immature dendritic cells (DC) ingesting C1q-bound autologous apoptotic cells (AC) (C1q-polarized DC) increase secretion of anti-inflammatory cytokines such as IL-10 and reduce pro-inflammatory cytokines such as TNFα. In this study, we demonstrate that C1q-polarized DC express significantly more surface PD-L2 and CD39 and significantly less CD86 relative to DC ingesting AC alone. To elucidate whether C1q-polarized DC functionally modulate the adaptive immune responses, human autologous T cells were incubated with DC or C1q-polarized DC and the proliferation and induction of CD4+ and CD8+ T cell subset was assessed. We discovered that relative to DC ingesting AC in the absence of C1q, C1q-polarized DC decrease autologous Th17 proliferation and induction and Th1 proliferation when the T cells were maintained in IL-7 prior to the MLR. These data imply that C1q-polarized DC can switch T cell function to reduce T effector cell activation and/or suppress the induction of autoimmunity, identifying new potential pathways for therapeutic intervention in SLE and other inflammatory diseases.