| First Author | Jiang S | Year | 2018 |
| Journal | Cell Metab | Volume | 27 |
| Issue | 2 | Pages | 393-403.e4 |
| PubMed ID | 29337138 | Mgi Jnum | J:257457 |
| Mgi Id | MGI:6119916 | Doi | 10.1016/j.cmet.2017.12.007 |
| Citation | Jiang S, et al. (2018) Let-7 Suppresses B Cell Activation through Restricting the Availability of Necessary Nutrients. Cell Metab 27(2):393-403.e4 |
| abstractText | The control of uptake and utilization of necessary extracellular nutrients-glucose and glutamine-is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production. Both overexpression and deletion of let-7 in this cluster leads to altered TI-IgM production. Mechanistically, let-7adf suppresses the acquisition and utilization of key nutrients, including glucose and glutamine, through directly targeting hexokinase 2 (Hk2) and by repressing a glutamine transporter Slc1a5 and a key degradation enzyme, glutaminase (Gls), a mechanism mediated by regulation of c-Myc. Our results suggest a novel role of let-7adf as a "metabolic brake" on B cell antibody production. |
