The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Identification of Natural RORγ Ligands that Regulate the Development of Lymphoid Cells
Open accessAbstract
SUMMARY Mice deficient in the nuclear hormone receptor RORγt have defective development of thymocytes, lymphoid organs, Th17 cells and type 3 innate lymphoid cells. RORγt binds to oxysterols derived from cholesterol catabolism but it is not clear whether these are its natural ligands. Here, we show that sterol lipids are necessary and sufficient to drive RORγt-dependent transcription. We combined overexpression, RNA interference and genetic deletion of metabolic enzymes to study RORγ-dependent transcription. Our results are consistent with the RORγt ligand(s) being a cholesterol biosynthetic intermediate (CBI) downstream of lanosterol and upstream of zymosterol. Analysis of lipids bound to RORγ identified molecules with molecular weights consistent with CBIs. Furthermore, CBIs stabilized the RORγ ligand-binding domain and induced co-activator recruitment. Genetic deletion of metabolic enzymes upstream of the RORγt-ligand(s) affected the development of lymph nodes and Th17 cells. Our data suggest that CBIs play a role in lymphocyte development potentially through regulation of RORγt.
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Metadata
- Authors
- Santori, F. R., Huang, P., van de Pavert, S. A., Douglass, E. F., Leaver, D. J., Haubrich, B. A., Keber, R., Lorbek, G., Konijn, T., Rosales, B. N., Rozman, D., Horvat, S., Rahier, A., Mebius, R. E., Rastinejad, F., Nes, W. D., & Littman, D. R.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 21
- Issue
- 2
- Pages
- 286-298
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2125786873
- Cited by
- 235
- References
- 11
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Santori, F. R., Huang, P., van de Pavert, S. A., Douglass, E. F., Leaver, D. J., Haubrich, B. A., Keber, R., Lorbek, G., Konijn, T., Rosales, B. N., Rozman, D., Horvat, S., Rahier, A., Mebius, R. E., Rastinejad, F., Nes, W. D., & Littman, D. R. (2015). Identification of Natural RORγ Ligands that Regulate the Development of Lymphoid Cells. Cell Metabolism. https://doi.org/10.1016/j.cmet.2015.01.004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
