FcγRI (CD64) contributes to the severity of immune inflammation through regulating NF-κB/NLRP3 inflammasome pathway

Aims: Fc gamma receptor I (Fc gamma RI/CD64) that is restrictedly expressed on monocytes and macrophages, acts as the single high-affinity receptor of immunoglobulin G (IgG) in human. The expression of Fc gamma RI is positively correlated with immune inflammation. The primary aim of this study was to explore the effects of Fc gamma RI expression on immune-related inflammatory response and investigate the potential mechanisms. Main methods: Fc gamma RI-expressing Ba/F3 cells are the ideal models for evaluating the functions of Fc gamma RI. Nuclear factor kappa B (NF-kappa B) and NOD-like receptor protein 3 (NLRP3) inflammasome-associated protein expressions and inflammatory cytokine (IL-1 beta and IL-18) release were detected in the presence or absence of NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC). Besides, the effects of Fc gamma RI on the activation of the NLRP3 inflammasomes were also investigated in THP-1 macrophages deficient for Fc gamma RI. Key findings: Fc gamma RI-expressing Ba/F3 cells appeared increased NLRP3 inflammasome formation and IL-1 beta and IL-18 release via activating NF-kappa B signaling. Interestingly, this alteration could be reversed in THP-1 macrophages after Fc gamma RI was silenced. Significance: These results indicated that Fc gamma RI functioned as a regulator for immune inflammation via acceleration of NF-kappa B regulating NLRP3 inflammasome signaling.