Citrullination is a post-translational modification mediated by peptidylarginine deiminases (PADs) that deiminate arginine residues. A greater abundance of citrullinated peptides is associated with joint inflammation in rheumatoid arthritis (RA). In Science Immunology, Sun et al. show that the transcription factor NF-κB is modified by arginine citrullination in neutrophils, which express high amounts of PADs. This modification leads to enhanced NF-κB interaction with the nuclear import factor importin-a3 and increased expression of the proinflammatory mediators tumor necrosis factor (TNF) and interleukin 1β (IL-1β). In vitro inhibition of PAD activity in lipopolysaccharide-activated human neutrophils reduces nuclear translocation of the NF-κB p65 (RelA) subunit and attenuates expression of both TNF and IL-1β. It remains to be determined whether inhibition of PAD would be beneficial in vivo or would restrict NF-κB-mediated negative feedback and resolution of inflammation.

Sci. Immunol. 2, eaal3062 (2017)