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Rheumatoid arthritis

Growing role for PADs in pathogenesis

Nature Reviews Rheumatology volume 13, page 450 (2017)Cite this article

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Researchers Bo Sun and Nishant Dwivedi, together with their colleagues, characterized a novel relationship between PAD4 and the transcription factor NF-κB. Citrullination of the p65 subunit of NF-κB by PAD4 increased the binding of this subunit to importin α3 in neutrophils, thereby increasing the rate of nuclear translocation of NF-κB and the subsequent production of the pro-inflammatory cytokines IL-1β and TNF. “Our data set an example of how citrullination can directly modulate the function of transcription factors and immune cells,” says I-Cheng Ho, corresponding author on the study. “By promoting the expression of inflammatory cytokines, such as TNF and IL-1β, hypercitrullination can also actively contribute to the pathogenesis of RA,” he continues.

A haplotype of PADI4, which encodes PAD4, is a known risk factor for RA

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References

  1. Sun, B. et al. Citrullination of NF-κB p65 promotes its nuclear localization and TLR-induced expression of IL-1β and TNFα. Sci. Immunol. 2, eaal3062 (2017)

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  1. Joanna Collison
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Collison, J. Growing role for PADs in pathogenesis. Nat Rev Rheumatol 13, 450 (2017). https://doi.org/10.1038/nrrheum.2017.108

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