Cell-based high throughput screening identified a novel compound that promotes regulatory T cells and prevents autoimmune colitis.

Cell-based high throughput screening identified a novel compound that promotes regulatory T cells and prevents autoimmune colitis. Biochem Pharmacol. 2019 Aug 23;: Authors: Mao R, Liu H, Yi B, Purohit S, Kuczma M, Kraj P, She JX Abstract Regulatory T cells (TR) show great promise for treating autoimmune diseases, allergies and preventing transplant rejection; however, their clinical application has been hampered by the lack of efficient ex vivo or in vivo expansion strategies. Here we report screening data on 130,000 low molecular weight (LMW) compounds for their TR promoting potential using a self-developed high-throughput cell-based assay. One of the lead compounds, an isoxazolecarboxamide designated as TRP38, efficiently converts naïve CD4+ T cells to TR cells in vitro and protects mice from autoimmune colitis in vivo. In addition, TRP38 can synergize with other compounds and/or cytokines such as rapamycin and TGFβ for TR conversion, probably via directly inhibiting P70s6 phosphorylation without affecting mTOR expression, underscoring the importance of complementary and coordinated activity of multiple signaling pathways for the increased level of stable TR cell production. PMID: 31449782 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research