The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
GCN2 Kinase in T Cells Mediates Proliferative Arrest and Anergy Induction in Response to Indoleamine 2,3-Dioxygenase
Open accessAbstract
Indoleamine 2,3 dioxygenase (IDO) catabolizes the amino acid tryptophan. IDO-expressing immunoregulatory dendritic cells (DCs) have been implicated in settings including tumors, autoimmunity, and transplant tolerance. However, the downstream molecular mechanisms by which IDO functions to regulate T cell responses remain unknown. We now show that IDO-expressing plasmacytoid DCs activate the GCN2 kinase pathway in responding T cells. GCN2 is a stress-response kinase that is activated by elevations in uncharged tRNA. T cells with a targeted disruption of GCN2 were not susceptible to IDO-mediated suppression of proliferation in vitro. In vivo, proliferation of GCN2-knockout T cells was not inhibited by IDO-expressing DCs from tumor-draining lymph nodes. IDO induced profound anergy in responding wild-type T cells, but GCN2-knockout cells were refractory to IDO-induced anergy. We hypothesize that GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by IDO.
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Citations
Cites
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341
Self-citationHarding, H. P., Zhang, Y., Bertolotti, A., Zeng, H., & Ron, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80330-5 · Cited by 2,021
Self-citationMunn, D. H., Sharma, M. D., Hou, D., Baban, B., Lee, J. R., Antonia, S. J., Messina, J. L., Chandler, P., Koni, P. A., & Mellor, A. L. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21583 · Cited by 852
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Cited by
Human nutrition, the gut microbiome and the immune system
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., & Gordon, J. I. (2011) · Nature · doi:10.1038/nature10213 · Cited by 2,588
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond
Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0016-5 · Cited by 1,586
Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health
Cervenka, I., Agudelo, L. Z., & Ruas, J. L. (2017) · Science · doi:10.1126/science.aaf9794 · Cited by 1,382
Targeting neoantigens to augment antitumour immunity
Yarchoan, M., Johnson, B. A., Lutz, E. R., Laheru, D. A., & Jaffee, E. M. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.154 · Cited by 997
Indoleamine 2,3 dioxygenase and metabolic control of immune responses
Munn, D. H., & Mellor, A. L. (2013) · Trends in Immunology · doi:10.1016/j.it.2012.10.001 · Cited by 1,037
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Metadata
- Authors
- Munn, D. H., Sharma, M. D., Baban, B., Harding, H. P., Zhang, Y., Ron, D., & Mellor, A. L.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 22
- Issue
- 5
- Pages
- 633-642
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2010378562
- Cited by
- 1,272
- References
- 3
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Munn, D. H., Sharma, M. D., Baban, B., Harding, H. P., Zhang, Y., Ron, D., & Mellor, A. L. (2005). GCN2 Kinase in T Cells Mediates Proliferative Arrest and Anergy Induction in Response to Indoleamine 2,3-Dioxygenase. Immunity. https://doi.org/10.1016/j.immuni.2005.03.013
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