| First Author | Seki SM | Year | 2020 |
| Journal | Sci Signal | Volume | 13 |
| Issue | 655 | PubMed ID | 33109748 |
| Mgi Jnum | J:354875 | Mgi Id | MGI:6751850 |
| Doi | 10.1126/scisignal.aay9217 | Citation | Seki SM, et al. (2020) Modulation of PKM activity affects the differentiation of TH17 cells. Sci Signal 13(655) |
| abstractText | Small molecules that promote the metabolic activity of the pyruvate kinase isoform PKM2, such as TEPP-46 and DASA-58, limit tumorigenesis and inflammation. To understand how these compounds alter T cell function, we assessed their therapeutic activity in a mouse model of T cell-mediated autoimmunity that mimics multiple sclerosis (MS). TH17 cells are believed to orchestrate MS pathology, in part, through the production of two proinflammatory cytokines: interleukin-17 (IL-17) and GM-CSF. We found that both TEPP-46 and DASA-58 suppressed the development of IL-17-producing TH17 cells but increased the generation of those producing GM-CSF. This switch redirected disease pathology from the spinal cord to the brain. In addition, we found that activation of PKM2 interfered with TGF-beta1 signaling, which is necessary for the development of TH17 and regulatory T cells. Collectively, our data clarify the therapeutic potential of PKM2 activators in MS-like disease and how these agents alter T cell function. |
