mTOR inhibitor INK128 attenuates dextran sodium sulfate-induced colitis by promotion of MDSCs on Treg cell expansion.
Guoping ShiDan LiJing RenXiaojing LiTingting WangHuan DouYayi HouPublished in: Journal of cellular physiology (2018)
Accumulating evidence has shown that mammalian target of rapamycin (mTOR) pathway and myeloid-derived suppressor cells (MDSCs) are involved in pathogenesis of inflammatory bowel diseases (IBDs). INK128 is a novel mTOR kinase inhibitor in clinical development. However, the exact roles of MDSCs and INK128 in IBD are unclear. Here, we showed that the INK128 treatment enhanced the resistance of mice to dextran sodium sulfate (DSS)-induced colitis and inhibited the differentiation of MDSCs into macrophages. Moreover, interferon (IFN)-α level was elevated in INK128-treated colitis mice. When stimulated with IFN-α in vitro, MDSCs showed a superior immunosuppression activity. Of note, the regulatory T cells (Tregs) increased but Th1 cells decreased in INK128-treated colitis mice. These results indicate that mTOR inhibitor INK128 attenuates DSS-induced colitis via Treg expansion promoted by MDSCs. Our work provides a new evidence that INK128 is potential to be a therapeutic drug on DSS-induced colitis via regulating MDSCs as well as maintaining Treg expansion.
Keyphrases
- regulatory t cells
- dendritic cells
- induced apoptosis
- cell proliferation
- immune response
- cell cycle arrest
- high fat diet induced
- emergency department
- single cell
- type diabetes
- metabolic syndrome
- endoplasmic reticulum stress
- mesenchymal stem cells
- cell death
- cell therapy
- climate change
- density functional theory
- wild type
- drug induced