title: Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ.
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.
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Brian
authors: B
authors: Astry
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Shivaprasad H
authors: SH
authors: Venkatesha
authors: Molecular Immunology and Inflammation Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Arian
authors: A
authors: Laurence
authors: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Aaron
authors: A
authors: Christensen-Quick
authors: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Alfredo
authors: A
authors: Garzino-Demo
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Matthew B
authors: MB
authors: Frieman
authors: Molecular Immunology and Inflammation Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: John J
authors: JJ
authors: O'Shea
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: kmoudgil@som.umaryland.edu.
authors: Kamal D
authors: KD
authors: Moudgil
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid; D001327:Autoimmune Diseases / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology; D053978:Pentacyclic Triterpenes; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol
keywords: Celastrol;; Chinese medicine;; Experimental arthritis;; Immune regulation; Rheumatoid arthritis;; T helper 17 cells;; T regulatory cells;