Astry Brian, Venkatesha Shivaprasad H, Laurence Arian, Christensen-Quick Aaron, Garzino-Demo Alfredo, Frieman Matthew B, O'Shea John J, Moudgil Kamal D
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Clin Immunol. 2015 Apr;157(2):228-38. doi: 10.1016/j.clim.2015.01.011. Epub 2015 Feb 7.
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.
炎症是自身免疫性关节炎的一个重要组成部分。致病性辅助性T细胞17(Th17)和保护性调节性T细胞(Treg)之间的平衡会影响疾病的严重程度,而重新调整这种平衡为控制自身免疫提供了一种有吸引力的方法。我们确定了佐剂性关节炎(AA)大鼠关节中Th17和Treg的频率,AA是类风湿性关节炎(RA)的一种模型。我们还研究了雷公藤红素(一种来自传统中药南蛇藤的生物活性化合物,可抑制AA)对关节中Th17/Treg平衡的影响。雷公藤红素治疗可减少关节中的Th17细胞,但增加Treg细胞,并且它通过阻断pSTAT3的激活在体外抑制Th17分化但促进Treg分化。此外,雷公藤红素限制了Th17分化细胞因子和趋化因子(CCL3、CCL5)的产生。因此,雷公藤红素部分地通过改变炎症关节中的Th17/Treg比例来抑制关节炎,并且应该作为RA治疗的潜在辅助/替代药物进行测试。