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

doi:10.1016/j.clim.2015.01.011

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

Dermatology

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	228-238
Number of pages	11
Journal	Clinical Immunology
Volume	157
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2015.01.011
State	Published - 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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10.1016/j.clim.2015.01.011

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Astry, B., Venkatesha, S. H., Laurence, A., Christensen-Quick, A., Garzino-demo, A., Frieman, M. B., O'Shea, J. J., & Moudgil, K. D. (2015). Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ. Clinical Immunology, 157(2), 228-238. https://doi.org/10.1016/j.clim.2015.01.011

Astry, B, Venkatesha, SH, Laurence, A, Christensen-Quick, A, Garzino-demo, A, Frieman, MB, O'Shea, JJ & Moudgil, KD 2015, 'Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ', Clinical Immunology, vol. 157, no. 2, pp. 228-238. https://doi.org/10.1016/j.clim.2015.01.011

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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.",

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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: {\textcopyright} 2015 Elsevier Inc.",

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AU - Garzino-demo, Alfredo

AU - Frieman, Matthew B.

AU - O'Shea, John J.

AU - Moudgil, Kamal D.

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N2 - 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.

AB - 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.

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

Abstract

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