Inhibiting RORγt/Th17 axis for autoimmune disorders

T-Helper 17 Cell Polarization in Pulmonary Arterial Hypertension

“…14 Lastly, several lymphocyte populations dedicated to the inhibition of autoimmune reaction or to regulation of the T-cell response (regulatory T cells, natural killer, and natural killer T cells) [37][38][39] are decreased in number and in function in pulmonary hypertension. 11,[40][41][42] Autoimmune diseases oft en result from the imbalance between regulatory T and Th 17 cells producing IL-17, and this balance is impaired in nearly all clinical conditions, thus making the therapeutic target of Th 17 signaling a promising treatment in chronic infl ammation, 25,43 and possibly in PAH, according to our results.…”

Discovery of N -(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORγt inverse agonists

“…5 RORt inhibitors has potential utility in reducing the activity of Th17 cells and therefore can be developed as therapeutic agents for the treatment of Th17-mediated autoimmune diseases. [7][8][9][10][11][12][13] A few small molecule inhibitors against RORt have been reported in literature. 14 Digoxin, 15 SR1001 16 and Ursolic acid 17 were firstly reported to inhibit RORt and ameliorate EAE in mice via intraperitoneal administration.…”

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

“…Several new selective and more potent RORγt inhibitors have since been described [177], whilst JMJD3 inhibitors have also been shown to indirectly regulate expression of RORγt [48]. Clinically, RORγt-targeted agents are suggested to have potential utility within the autoimmune setting.…”