GSE102728 IgG immunocomplexes sensitize human monocytes for inflammatory hyperactivity via transcriptomic and epigenetic reprogramming in autoimmune disease

We present here evidence that IgG ICs precipitated from RA sera sensitized human monocytes for a long-lasting inflammatory functional state characterized by a strong TNF α response to cellular proteins representing damage-associated molecular patterns (DAMPs) and microbe-derived pathogen-associated molecular patterns (PAMPs). Importantly, plate-coated human IgG (cIgG, a mimic of deposited IC without antigen restriction) exhibited similarly robust ability of monocyt e sensitization in vitro. The cIgG-induced functional programming is through FcγRIIa/Syk signaling and accompanied by characteristic phenotypic changes, readjustment of autocrine feed-forward and feedback regulatory loops with dynamic shift in the transcription factor repertoire and epigenetic modi fication of various inflammatory cytokine genes. Moreover, macrophages freshly isolated from synovia of patients with RA, but not sera-negative arthropathy, displayed signature gene expression profile highly similar to that of IC-sensitized human monocytes, indicative of historical priming events by IgG ICs in vivo. Thus, the ability of IgG ICs to drive sustainable functional sensitization/reprogramming of monocytes and macrophages towards inflammation may render them key players in the development of chronic inflammatory autoimmune diseases.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research