ArticleCell metabolism2015
Identification of natural RORγ ligands that regulate the development of lymphoid cells.
Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed.
- Preclinical and clinical characterization of the RORγt inhibitor JNJ-61803534.Scientific reports · 2021Trial
- A dysbiotic microbiome triggers TScience translational medicine · 2018Trial
- Unconventional role of hydroxymethylglutaryl-CoA synthase 1 in driving pathogenic TScience advances · 2026Article
- An Acetylation-Primed SUMOylation Switch Controls RORβ Stability through a p300-SIRT1 Regulatory Axis.Research square · 2026Article
- Acetylation-Primed SUMOylation Drives RORβ Turnover via a p300-SIRT1 Regulatory Axis.bioRxiv : the preprint server for biology · 2026Article
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Energy-sensing molecule RORγ regulates cholesterol metabolism and immune signaling in diabetic kidney disease and aging.Nature communications · 2026Article
- Inhibition of the RORC/GPX4 mediated ferroptosis regulatory axis suppresses tumor growth and alleviates enzalutamide resistance in prostate cancer.Cellular & molecular biology letters · 2026Article
- Divergent immunometabolic reprogramming in psoriasis and atopic dermatitis: a tale of two inflammatory skin diseases.Frontiers in immunology · 2026Review
- 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility.Genome biology · 2025Article
- Cellular metabolism in Th9, Th17, and Treg cell differentiation.International immunology · 2025Review
- Integrative bioinformatics analysis unveils hub transcription factors and their interacting drugs in immunoglobulin A nephropathy: Implications for pathogenesis and treatments.Journal, genetic engineering & biotechnology · 2025Article
- Identification of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ).Journal of natural products · 2025Article
- Acsbg1 regulates differentiation and inflammatory properties of CD4+ T cells.European journal of microbiology & immunology · 2025Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- Emerging Therapeutic Targets in Rheumatoid Arthritis: Focusing on HIF-1α, Nrf2, STATs, and RORγt.Current drug targets · 2025Review
- Fine-tuning immunity: ubiquitin-dependent regulation of interleukin-17A expression by Th17 cells.Frontiers in immunology · 2025Review
- Deciphering the deterministic role of TCR signaling in T cell fate determination.Frontiers in immunology · 2025Review
- Cholesterol sensing and metabolic adaptation in tissue immunity.Trends in immunology · 2024Review
- Knockouts ofiScience · 2024Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
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, RNAi, 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 coactivator 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.