Serological type I interferon promotes AIM2 inflammasome dysregulation in lupus patients
The Absent in Melanoma 2 (AIM2) inflammasome is a crucial producer of IL-1beta and IL-18 upon double-stranded (ds)DNA sensing but its role in SLE remains ambiguous. We aimed to investigate the involvement and underlying mechanism leading to AIM2 inflammasome dysregulation in lupus patients. Serological factors leading to the perturbed AIM2 inflammasome response was tested by in vitro culture of primary monocytes. SLE patients' sera and recombinant interferon (IFN)-alpha could promote AIM2 inflammasome activity by augmenting AIM2 expression. We compared the transcriptome profile changes in primary human monocytes upon exposure to SLE serum and type I interferon by RNA-seq. Our findings revealed a novel pathway by which serological type I IFN propagates innate immune dysfunction in SLE via the STAT1-STAT2/AIM2 inflammasome axis in monocytes. Overall design: Comparative gene expression profiling analysis of RNA-seq data in healthy human monocytes upon SLE serum stimulation (vs. HC serum stimulation) and type I IFN stimulation (vs. untreated control). Each treatment group consists of three biological replicates.