| First Author | Yang J | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 11 | Pages | 12780-12799 |
| PubMed ID | 31480861 | Mgi Jnum | J:290401 |
| Mgi Id | MGI:6436201 | Doi | 10.1096/fj.201900863R |
| Citation | Yang J, et al. (2019) T-cell-derived extracellular vesicles regulate B-cell IgG production via pyruvate kinase muscle isozyme 2. FASEB J 33(11):12780-12799 |
| abstractText | Intercellular communication between lymphocytes plays a fundamental role in numerous immune responses. Previously, we demonstrated that hyperhomocysteinemia (HHcy) induced T cell intracellular glycolytic-lipogenic reprogramming and IFN-gamma secretion via pyruvate kinase muscle isozyme 2 (PKM2) to accelerate atherosclerosis. Usually, B cells partially obtain help from T cells in antibody responses. However, whether PKM2 activation in T cells regulates B cell antibody production is unknown. Extracellular vesicles (EVs) are important cellular communication vehicles. Here, we found that PKM2 activator TEPP46-stimulated T-cell-derived EVs promoted B-cell IgG secretion. Conversely, EVs secreted from PKM2-null T cells were internalized into B cells and markedly inhibited B-cell mitochondrial programming, activation, and IgG production. Mechanistically, lipidomics analyses showed that increased ceramides in PKM2-activated T-cell EVs were mainly responsible for enhanced B cell IgG secretion induced by these EVs. Finally, quantum dots (QDs) were packaged with PKM2-null T cell EVs and anti-CD19 antibody to exert B-cell targeting and inhibit IgG production, eventually ameliorating HHcy-accelerated atherosclerosis in vivo. Thus, PKM2-mediated EV ceramides in T cells may be an important cargo for T-cell-regulated B cell IgG production, and QD-CD19-PKM2-null T cell EVs hold high potential to treat B cell overactivation-related diseases.-Yang, J., Dang, G., Lu, S., Liu, H., Ma, X., Han, L., Deng, J., Miao, Y., Li, X., Shao, F., Jiang, C., Xu, Q., Wang, X., Feng, J. T-cell-derived extracellular vesicles regulate B-cell IgG production via pyruvate kinase muscle isozyme 2. |
