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Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4 T Cells.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4 T Cells."

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.

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Journal Details

This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 129-141.e4

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