Nature Communications (Oct 2019)

HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis

  • Chao Liang,
  • Jie Li,
  • Cheng Lu,
  • Duoli Xie,
  • Jin Liu,
  • Chuanxin Zhong,
  • Xiaohao Wu,
  • Rongchen Dai,
  • Huarui Zhang,
  • Daogang Guan,
  • Baosheng Guo,
  • Bing He,
  • Fangfei Li,
  • Xiaojuan He,
  • Wandong Zhang,
  • Bao-Ting Zhang,
  • Ge Zhang,
  • Aiping Lu

DOI
https://doi.org/10.1038/s41467-019-12163-z
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 13

Abstract

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Leflunomide is used for the treatment of rheumatoid arthritis. Here, the authors show that effectiveness is limited in patients with higher levels of serum c-reactive protein (CRP). Using animal models, they show that higher CRP induces HIF1a expression, which in turn interferes with Leflunomide signalling, and that effectiveness of the drug is restored when HIF1a is pharmacologically inhibited.