Celastrol ameliorates autoimmune disorders in Trex1-deficient mice

Biochem Pharmacol. 2020 Aug:178:114090. doi: 10.1016/j.bcp.2020.114090. Epub 2020 Jun 19.


Celastrol is one of most potent bioactive molecule isolated from the medicinal plant Tripterygium wilfordii (Thunder God Vine) and is well known for its potential therapeutic value against various chronic diseases including the autoimmune diseases, such as systemic lupus erythematosus and Aicardi-Goutieres syndrome, or other interferonopathies. However, the underlying mechanism of celastrol function remains unclear. Here we showed that celastrol caused inhibition of interferon regulatory factor 3 (IRF3) activation leading to the down-regulation of the interferon response triggered by cytosolic nucleic acids in vitro and in vivo. Moreover, celastrol treatment markedly ameliorates the autoimmune phenotypes including myocarditis, aberrant interferon response and autoantibody production, as well as the excessive T-cell activation in Trex1-/- autoimmune disease mouse model. Collectively, our results indicate that celastrol inhibits interferon response by targeting IRF3 activation and may be used as an effective treatment for interferon response-dependent autoimmune diseases.

Keywords: Autoimmunity; Celastrol; IRF3; Interferon; Trex1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / metabolism*
  • Dose-Response Relationship, Drug
  • Exodeoxyribonucleases / deficiency*
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pentacyclic Triterpenes
  • Phosphoproteins / deficiency*
  • RAW 264.7 Cells
  • Random Allocation
  • Tripterygium*
  • Triterpenes / isolation & purification
  • Triterpenes / therapeutic use*


  • Pentacyclic Triterpenes
  • Phosphoproteins
  • Triterpenes
  • Exodeoxyribonucleases
  • three prime repair exonuclease 1
  • celastrol