The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism
Open accessAbstract
SUMMARY Activated T cells differentiate into functional subsets with distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to support the tricarboxylic acid cycle and redox and epigenetic reactions. Here, we identify a key role for GLS in T cell activation and specification. Though GLS deficiency diminished initial T cell activation and proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet to promote differentiation and effector function of CD4 Th1 and CD8 CTL cells. This was associated with altered chromatin accessibility and gene expression, including decreased PIK3IP1 in Th1 cells that sensitized to IL-2-mediated mTORC1 signaling. In vivo, GLS null T cells failed to drive Th17-inflammatory diseases, and Th1 cells had initially elevated function but exhausted over time. Transient GLS inhibition, however, led to increased Th1 and CTL T cell numbers. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation.
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“In addition to increased use of glucose in activated effector T cells, glutamine uptake andglutaminolysis are also upregulated (Carr et al., 2010; Wang et al., 2011).”
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Navigating metabolic pathways to enhance antitumour immunity and immunotherapy
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Metadata
- Authors
- Johnson, M. O., Wolf, M. M., Madden, M. Z., Andrejeva, G., Sugiura, A., Contreras, D. C., Maseda, D., Liberti, M. V., Paz, K., Kishton, R. J., Johnson, M. E., de Cubas, A. A., Wu, P., Li, G., Zhang, Y., Newcomb, D. C., Wells, A. D., Restifo, N. P., Rathmell, W. K., Locasale, J. W., Davila, M. L., Blazar, B. R., & Rathmell, J. C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 175
- Issue
- 7
- Pages
- 1780-1795.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2899010137
- Cited by
- 715
- References
- 17
- FWCI
- 21.63
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Johnson, M. O., Wolf, M. M., Madden, M. Z., Andrejeva, G., Sugiura, A., Contreras, D. C., Maseda, D., Liberti, M. V., Paz, K., Kishton, R. J., Johnson, M. E., de Cubas, A. A., Wu, P., Li, G., Zhang, Y., Newcomb, D. C., Wells, A. D., Restifo, N. P., Rathmell, W. K., . . . Rathmell, J. C. (2018). Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism. Cell. https://doi.org/10.1016/j.cell.2018.10.001
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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