Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ

Brian Astry, Shivaprasad H. Venkatesha, Arian Laurence, Aaron Christensen-Quick, Alfredo Garzino-demo, Matthew B. Frieman, John J. O'Shea, Kamal D. Moudgil

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Inflammation is an integral component of autoimmune arthritis. The balance of pathogenic T helper 17 (Th17) and protective T regulatory (Treg) cells can influence disease severity, and its resetting offers an attractive approach to control autoimmunity. We determined the frequency of Th17 and Treg in the joints of rats with adjuvant arthritis (AA), a model of rheumatoid arthritis (RA). We also investigated the impact of Celastrol, a bioactive compound from the traditional Chinese medicine Celastrus that can suppress AA, on Th17/Treg balance in the joints. Celastrol treatment reduced Th17 cells but increased Treg in the joints, and it inhibited Th17 differentiation but promoted Treg differentiation in vitro by blocking the activation of pSTAT3. Furthermore, Celastrol limited the production of Th17-differentiating cytokines and chemokines (CCL3, CCL5). Thus, Celastrol suppressed arthritis in part by altering Th17/Treg ratio in inflamed joints, and it should be tested as a potential adjunct/alternative for RA therapy.

Original languageEnglish (US)
Pages (from-to)228-238
Number of pages11
JournalClinical Immunology
Volume157
Issue number2
DOIs
StatePublished - Apr 1 2015

Bibliographical note

Funding Information:
This work was supported by NIH grants R01 AT004321 and F31 AT007278 . We thank Krystal Matthews for her help with the NF-κB reporter assay; Joao Pedra for advice in the testing of mature IL-1β; Qing Chen for help with testing of the composition of synovial-infiltrating cells; and Stefanie Vogel for providing the qRT-PCR facility.

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

  • Celastrol;
  • Chinese medicine
  • Experimental arthritis;
  • Immune regulation
  • Rheumatoid arthritis;
  • T helper 17 cells;
  • T regulatory cells;

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