Analysis of SLE monocytes stimulated with cGAS-STING agonist
Enhanced interferon alpha (IFNa) production has been implicated in the pathogenesis of systemic lupus erythematosus(SLE). Previously, we reported that when human PBMCs were stimulated with 2'3'-cGAMP, monocytes but not pDCs, were the major producers of IFNa. In addition, monocytes from SLE patients had enhanced IFNa production upon activation of the STING pathway, and this was positively correlated with SLE disease activity. We aimed to elucidate the underlying molecular mechanism responsible for the enhanced IFNa production in SLE monocytes. Monocytes from SLE patients and HC were stimulated with 2'3'-cyclic GAMP(2'3'-cGAMP), a ligand of STING for 5h. HC monocytes were pretreated with IFNa (100 U/ml) for 18h prior to the stimulation with 2'3'-cGAMP. IFNa positive/negative cells were labeled by using a secretion assay method and RNA-seq was performed in these cell populations.