The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
mTOR coordinates transcriptional programs and mitochondrial metabolism of activated Treg subsets to protect tissue homeostasis
Open accessAbstract
Regulatory T (T reg) cells derived from the thymus (tT reg) and periphery (pT reg) have central and distinct functions in immunosuppression, but mechanisms for the generation and activation of T reg subsets in vivo are unclear. Here, we show that mechanistic target of rapamycin (mTOR) unexpectedly supports the homeostasis and functional activation of tT reg and pT reg cells. mTOR signaling is crucial for programming activated T reg-cell function to protect immune tolerance and tissue homeostasis. T reg-specific deletion of mTOR drives spontaneous effector T-cell activation and inflammation in barrier tissues and is associated with reduction in both thymic-derived effector T reg (eT reg) and pT reg cells. Mechanistically, mTOR functions downstream of antigenic signals to drive IRF4 expression and mitochondrial metabolism, and accordingly, deletion of mitochondrial transcription factor A (Tfam) severely impairs T reg-cell suppressive function and eT reg-cell generation. Collectively, our results show that mTOR coordinates transcriptional and metabolic programs in activated T reg subsets to mediate tissue homeostasis.
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Cites
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
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Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
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mTOR Signaling in Growth, Metabolism, and Disease
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Self-citationMichalek, R. D., Gerriets, V. A., Jacobs, S. R., Macintyre, A. N., MacIver, N. J., Mason, E. F., Sullivan, S. A., Nichols, A. G., & Rathmell, J. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003613 · Cited by 2,091
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Self-citationIndividual intestinal symbionts induce a distinct population of RORγ + regulatory T cells
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The microbiota regulates type 2 immunity through RORγt + T cells
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Cited by
T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
Desdín-Micó, G., Soto-Heredero, G., Aranda, J. F., Oller, J., Carrasco, E., Gabandé-Rodríguez, E., Blanco, E. M., Alfranca, A., Cussó, L., Desco, M., et al. (2020) · Science · doi:10.1126/science.aax0860 · Cited by 572
Saravia, J., Chapman, N. M., & Chi, H. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0220-6 · Cited by 489
Self-citationMetabolism as a guiding force for immunity
Jung, J., Zeng, H., & Horng, T. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0217-x · Cited by 346
Self-citationmTOR Regulation of Glycolytic Metabolism in T Cells
Salmond, R. J. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00122 · Cited by 211
mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions
Huang, H., Long, L., Zhou, P., Chapman, N. M., & Chi, H. (2020) · Immunological Reviews · doi:10.1111/imr.12845 · Cited by 193
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Metadata
- Authors
- Chapman, N. M., Zeng, H., Nguyen, T.-L. M., Wang, Y., Vogel, P., Dhungana, Y., Liu, X., Neale, G., Locasale, J. W., & Chi, H.
- Venue
- Nature Communications
- Published
- 2018-05-29
- Volume
- 9
- Issue
- 1
- Pages
- 2095-2095
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2805618319
- Cited by
- 192
- References
- 17
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chapman, N. M., Zeng, H., Nguyen, T.-L. M., Wang, Y., Vogel, P., Dhungana, Y., Liu, X., Neale, G., Locasale, J. W., & Chi, H. (2018). mTOR coordinates transcriptional programs and mitochondrial metabolism of activated Treg subsets to protect tissue homeostasis. Nature Communications. https://doi.org/10.1038/s41467-018-04392-5
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