| First Author | Previte DM | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 1 | Pages | 129-141.e4 |
| PubMed ID | 30943396 | Mgi Jnum | J:286111 |
| Mgi Id | MGI:6389955 | Doi | 10.1016/j.celrep.2019.03.004 |
| Citation | Previte DM, et al. (2019) Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4(+) T Cells. Cell Rep 27(1):129-141.e4 |
| abstractText | Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed by CD4(+) T cells and tempers their homeostatic expansion. Because CD4(+) T cell proliferation is tightly coupled to bioenergetics, we investigate the role of LAG-3 in modulating naive CD4(+) T cell metabolism. LAG-3 deficiency enhances the metabolic profile of naive CD4(+) T cells by elevating levels of mitochondrial biogenesis. In vivo, LAG-3 blockade partially restores expansion and the metabolic phenotype of wild-type CD4(+) T cells to levels of Lag3(-/-) CD4(+) T cells, solidifying that LAG-3 controls these processes. Lag3(-/-) CD4(+) T cells also demonstrate greater signal transducer and activator of transcription 5 (STAT5) activation, enabling resistance to interleukin-7 (IL-7) deprivation. These results implicate this pathway as a target of LAG-3-mediated inhibition. Additionally, enhancement of STAT5 activation, as a result of LAG-3 deficiency, contributes to greater activation potential in these cells. These results identify an additional mode of regulation elicited by LAG-3 in controlling CD4(+) T cell responses. |
