{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:28Z","timestamp":1787009008613,"version":"build-2736575974"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T00:00:00Z","timestamp":1717286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Among the T helper cell subsets, Th17 cells contribute to the development of various inflammatory and autoimmune diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Retinoid-related orphan receptor gamma t (ROR\u03b3t), a nuclear hormone receptor, serves as a master transcription factor for Th17 cell differentiation. Recent findings have shown that modulating the metabolic pathway is critical for Th17 cell differentiation, particularly through the engagement of de novo lipid biosynthesis. Suppression of lipid biosynthesis, either through the pharmacological inhibition or gene deletion of related enzymes in CD4+ T cells, results in significant impairment of Th17 cell differentiation. Mechanistic studies indicate that metabolic fluxes through both the fatty acid and cholesterol biosynthetic pathways have a pivotal role in the regulation of ROR\u03b3t activity through the generation of endogenous ROR\u03b3t lipid ligands. This review discusses recent discoveries highlighting the importance of lipid metabolism in Th17 cell differentiation and function, as well as exploring specific molecular pathways involved in ROR\u03b3t activation through cellular lipid metabolism. We further elaborate on a pioneering therapeutic approach to improve inflammatory and autoimmune disorders via the inhibition of ROR\u03b3t.<\/jats:p>","DOI":"10.1093\/intimm\/dxae031","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T17:44:38Z","timestamp":1717177478000},"page":"487-496","source":"Crossref","is-referenced-by-count":18,"title":["Lipid metabolism: a central modulator of ROR\u03b3t-mediated Th17 cell differentiation"],"prefix":"10.1093","volume":"36","author":[{"given":"Toshio","family":"Kanno","sequence":"first","affiliation":[{"name":"Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute , Kisarazu, Chiba 292-0818 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Miyako","sequence":"additional","affiliation":[{"name":"Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute , Kisarazu, Chiba 292-0818 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-1938","authenticated-orcid":false,"given":"Yusuke","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute , Kisarazu, Chiba 292-0818 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,2]]},"reference":[{"key":"2024091014261405200_CIT0001","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature18848","article-title":"The microbiota in adaptive immune homeostasis and disease","volume":"535","author":"Honda","year":"2016","journal-title":"Nature"},{"key":"2024091014261405200_CIT0002","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","article-title":"The IL-17 family of cytokines in health and disease","volume":"50","author":"McGeachy","year":"2019","journal-title":"Immunity"},{"key":"2024091014261405200_CIT0003","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nri.2017.50","article-title":"The dichotomous nature of T helper 17 cells","volume":"17","author":"Stockinger","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"2024091014261405200_CIT0004","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3109\/1547691X.2015.1115448","article-title":"Protective role of R381Q (rs11209026) polymorphism in IL-23R gene in immune-mediated diseases: a comprehensive review","volume":"13","author":"Abdollahi","year":"2016","journal-title":"J Immunotoxicol"},{"key":"2024091014261405200_CIT0005","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1126\/science.1135245","article-title":"A genome-wide association study identifies IL23R as an inflammatory bowel disease gene","volume":"314","author":"Duerr","year":"2006","journal-title":"Science"},{"key":"2024091014261405200_CIT0006","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nri.2017.99","article-title":"The spectrum of T cell metabolism in health and disease","volume":"18","author":"Bantug","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"2024091014261405200_CIT0007","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J Exp Med"},{"key":"2024091014261405200_CIT0008","doi-asserted-by":"crossref","first-page":"e148546","DOI":"10.1172\/JCI148546","article-title":"Targeting memory T cell metabolism to improve immunity","volume":"132","author":"Corrado","year":"2022","journal-title":"J Clin Invest"},{"key":"2024091014261405200_CIT0009","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s42255-018-0025-4","article-title":"ACC1 determines memory potential of individual CD4(+) T cells by regulating de novo fatty acid biosynthesis","volume":"1","author":"Endo","year":"2019","journal-title":"Nat Metab"},{"key":"2024091014261405200_CIT0010","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/intimm\/dxac025","article-title":"Fatty acid metabolism in T-cell function and differentiation","volume":"34","author":"Endo","year":"2022","journal-title":"Int Immunol"},{"key":"2024091014261405200_CIT0011","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.it.2014.12.005","article-title":"Fatty acid metabolism in the regulation of T cell function","volume":"36","author":"Lochner","year":"2015","journal-title":"Trends Immunol"},{"key":"2024091014261405200_CIT0012","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev-immunol-032712-095956","article-title":"Metabolic regulation of T lymphocytes","volume":"31","author":"MacIver","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"2024091014261405200_CIT0013","doi-asserted-by":"crossref","first-page":"13683","DOI":"10.1038\/ncomms13683","article-title":"Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARgamma directs early activation of T cells","volume":"7","author":"Angela","year":"2016","journal-title":"Nat Commun"},{"key":"2024091014261405200_CIT0014","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.celrep.2015.07.014","article-title":"Obesity drives Th17 cell differentiation by inducing the lipid metabolic kinase, ACC1","volume":"12","author":"Endo","year":"2015","journal-title":"Cell Rep"},{"key":"2024091014261405200_CIT0015","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ni.2570","article-title":"Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity","volume":"14","author":"Kidani","year":"2013","journal-title":"Nat Immunol"},{"key":"2024091014261405200_CIT0016","doi-asserted-by":"crossref","first-page":"109921","DOI":"10.1016\/j.celrep.2021.109921","article-title":"Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis","volume":"37","author":"Kanno","year":"2021","journal-title":"Cell Rep"},{"key":"2024091014261405200_CIT0017","doi-asserted-by":"crossref","first-page":"904875","DOI":"10.3389\/fimmu.2022.904875","article-title":"SCD2-mediated cooperative activation of IRF3-IRF9 regulatory circuit controls type I interferon transcriptome in CD4(+) T cells","volume":"13","author":"Kanno","year":"2022","journal-title":"Front Immunol"},{"key":"2024091014261405200_CIT0018","doi-asserted-by":"crossref","first-page":"e20210639","DOI":"10.1084\/jem.20210639","article-title":"ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice","volume":"218","author":"Nakajima","year":"2021","journal-title":"J Exp Med"},{"key":"2024091014261405200_CIT0019","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/ni.2386","article-title":"Metabolic checkpoints in activated T cells","volume":"13","author":"Wang","year":"2012","journal-title":"Nat Immunol"},{"key":"2024091014261405200_CIT0020","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cell.2012.09.016","article-title":"A validated regulatory network for Th17 cell specification","volume":"151","author":"Ciofani","year":"2012","journal-title":"Cell"},{"key":"2024091014261405200_CIT0021","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"2024091014261405200_CIT0022","doi-asserted-by":"crossref","first-page":"e003","DOI":"10.1621\/nrs.07003","article-title":"Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism","volume":"7","author":"Jetten","year":"2009","journal-title":"Nucl Recept Signal"},{"key":"2024091014261405200_CIT0023","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/ni.2027","article-title":"RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation","volume":"12","author":"Codarri","year":"2011","journal-title":"Nat Immunol"},{"key":"2024091014261405200_CIT0024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2016.07.004","article-title":"Post-translational regulation of RORgammat-A therapeutic target for the modulation of interleukin-17-mediated responses in autoimmune diseases","volume":"30","author":"Rutz","year":"2016","journal-title":"Cytokine Growth Factor Rev"},{"key":"2024091014261405200_CIT0025","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1096\/fj.13-242040","article-title":"RORalpha and ROR gamma are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D","volume":"28","author":"Slominski","year":"2014","journal-title":"FASEB J"},{"key":"2024091014261405200_CIT0026","doi-asserted-by":"crossref","first-page":"955","DOI":"10.4049\/jimmunol.1700457","article-title":"Regulation of Th17 differentiation by IKK\u03b1-dependent and -independent phosphorylation of ROR\u03b3t","volume":"199","author":"He","year":"2017","journal-title":"J Immunol"},{"key":"2024091014261405200_CIT0027","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-physiol-021909-135917","article-title":"Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics","volume":"72","author":"Huang","year":"2010","journal-title":"Annu Rev Physiol"},{"key":"2024091014261405200_CIT0028","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.4049\/jimmunol.0903586","article-title":"Glutamine uptake and metabolism are coordinately regulated by ERK\/MAPK during T lymphocyte activation","volume":"185","author":"Carr","year":"2010","journal-title":"J Immunol"},{"key":"2024091014261405200_CIT0029","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S1074-7613(02)00323-0","article-title":"The CD28 signaling pathway regulates glucose metabolism","volume":"16","author":"Frauwirth","year":"2002","journal-title":"Immunity"},{"key":"2024091014261405200_CIT0030","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cmet.2014.05.004","article-title":"The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function","volume":"20","author":"Macintyre","year":"2014","journal-title":"Cell Metab"},{"key":"2024091014261405200_CIT0031","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"2024091014261405200_CIT0032","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.4049\/jimmunol.180.7.4476","article-title":"Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways","volume":"180","author":"Jacobs","year":"2008","journal-title":"J Immunol"},{"key":"2024091014261405200_CIT0033","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nri3701","article-title":"Integrating canonical and metabolic signalling programmes in the regulation of T cell responses","volume":"14","author":"Pollizzi","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2024091014261405200_CIT0034","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"},{"key":"2024091014261405200_CIT0035","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri3198","article-title":"Regulation and function of mTOR signalling in T cell fate decisions","volume":"12","author":"Chi","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"2024091014261405200_CIT0036","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","article-title":"Activation of a metabolic gene regulatory network downstream of mTOR complex 1","volume":"39","author":"Duvel","year":"2010","journal-title":"Mol Cell"},{"key":"2024091014261405200_CIT0037","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.immuni.2013.09.015","article-title":"T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming","volume":"39","author":"Yang","year":"2013","journal-title":"Immunity"},{"key":"2024091014261405200_CIT0038","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cell.2008.04.052","article-title":"LXR signaling couples sterol metabolism to proliferation in the acquired immune response","volume":"134","author":"Bensinger","year":"2008","journal-title":"Cell"},{"key":"2024091014261405200_CIT0039","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/0092-8674(95)90193-0","article-title":"15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma","volume":"83","author":"Forman","year":"1995","journal-title":"Cell"},{"key":"2024091014261405200_CIT0040","doi-asserted-by":"crossref","first-page":"10207","DOI":"10.1073\/pnas.1733877100","article-title":"Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat\/high-carbohydrate diets","volume":"100","author":"Abu-Elheiga","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024091014261405200_CIT0041","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1242\/dmm.011338","article-title":"Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development","volume":"6","author":"Baenke","year":"2013","journal-title":"Dis Model Mech"},{"key":"2024091014261405200_CIT0042","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.cmet.2018.08.009","article-title":"The translational machinery of human CD4(+) T cells is poised for activation and controls the switch from quiescence to metabolic remodeling","volume":"28","author":"Ricciardi","year":"2018","journal-title":"Cell Metab"},{"key":"2024091014261405200_CIT0043","doi-asserted-by":"crossref","first-page":"S138","DOI":"10.1194\/jlr.R800079-JLR200","article-title":"Fatty acid metabolism: target for metabolic syndrome","volume":"50","author":"Wakil","year":"2009","journal-title":"J Lipid Res"},{"key":"2024091014261405200_CIT0044","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1172\/JCI63967","article-title":"Malonyl-CoA: the regulator of fatty acid synthesis and oxidation","volume":"122","author":"Foster","year":"2012","journal-title":"J Clin Invest"},{"key":"2024091014261405200_CIT0045","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41467-022-28417-2","article-title":"Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate","volume":"13","author":"Liu","year":"2022","journal-title":"Nat Commun"},{"key":"2024091014261405200_CIT0046","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/nri1650","article-title":"Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network","volume":"5","author":"Rosen","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"2024091014261405200_CIT0047","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1194\/jlr.R046458","article-title":"LPA receptor signaling: pharmacology, physiology, and pathophysiology","volume":"55","author":"Yung","year":"2014","journal-title":"J Lipid Res"},{"key":"2024091014261405200_CIT0048","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024091014261405200_CIT0049","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41586-024-07098-5","article-title":"IL-10 constrains sphingolipid metabolism to limit inflammation","volume":"627","author":"York","year":"2024","journal-title":"Nature"},{"key":"2024091014261405200_CIT0050","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41590-023-01691-y","article-title":"GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway","volume":"25","author":"Park","year":"2024","journal-title":"Nat Immunol"},{"key":"2024091014261405200_CIT0051","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nrm2335","article-title":"Lipid signalling in disease","volume":"9","author":"Wymann","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024091014261405200_CIT0052","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41467-024-44689-2","article-title":"Prostaglandin E(2) controls the metabolic adaptation of T cells to the intestinal microenvironment","volume":"15","author":"Villa","year":"2024","journal-title":"Nat Commun"},{"key":"2024091014261405200_CIT0053","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.3389\/fimmu.2017.01632","article-title":"Metabolism controls the balance of Th17\/T-regulatory cells","volume":"8","author":"Sun","year":"2017","journal-title":"Front Immunol"},{"key":"2024091014261405200_CIT0054","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/nm.3704","article-title":"De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells","volume":"20","author":"Berod","year":"2014","journal-title":"Nat Med"},{"key":"2024091014261405200_CIT0055","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1189\/jlb.3AB0417-159RR","article-title":"Fatty acid synthase regulates the pathogenicity of Th17 cells","volume":"102","author":"Young","year":"2017","journal-title":"J Leukoc Biol"},{"key":"2024091014261405200_CIT0056","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s00018-016-2399-3","article-title":"The obesity-related pathology and Th17 cells","volume":"74","author":"Endo","year":"2017","journal-title":"Cell Mol Life Sci"},{"key":"2024091014261405200_CIT0057","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2119\/molmed.2013.00113","article-title":"Fatty acid synthase inhibitor C75 ameliorates experimental colitis","volume":"20","author":"Matsuo","year":"2014","journal-title":"Mol Med"},{"key":"2024091014261405200_CIT0058","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.cmet.2019.10.004","article-title":"Lactate buildup at the site of chronic inflammation promotes disease by inducing CD4(+) T cell metabolic rewiring","volume":"30","author":"Pucino","year":"2019","journal-title":"Cell Metab"},{"key":"2024091014261405200_CIT0059","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1002\/eji.200838893","article-title":"Obesity predisposes to Th17 bias","volume":"39","author":"Winer","year":"2009","journal-title":"Eur J Immunol"},{"key":"2024091014261405200_CIT0060","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nm.3423","article-title":"Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity","volume":"20","author":"Kim","year":"2014","journal-title":"Nat Med"},{"key":"2024091014261405200_CIT0061","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1084\/jem.20082771","article-title":"The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity","volume":"206","author":"Klotz","year":"2009","journal-title":"J Exp Med"},{"key":"2024091014261405200_CIT0062","doi-asserted-by":"crossref","first-page":"7625","DOI":"10.4049\/jimmunol.0804192","article-title":"Regulation of Th17 differentiation by epidermal fatty acid-binding protein","volume":"182","author":"Li","year":"2009","journal-title":"J Immunol"},{"key":"2024091014261405200_CIT0063","doi-asserted-by":"crossref","first-page":"313","DOI":"10.4049\/jimmunol.179.1.313","article-title":"Deficiency of fatty acid-binding proteins in mice confers protection from development of experimental autoimmune encephalomyelitis","volume":"179","author":"Reynolds","year":"2007","journal-title":"J Immunol"},{"key":"2024091014261405200_CIT0064","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0079-6603(01)69048-2","article-title":"The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes","volume":"69","author":"Jetten","year":"2001","journal-title":"Prog Nucleic Acid Res Mol Biol"},{"key":"2024091014261405200_CIT0065","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev.biophys.30.1.329","article-title":"Binding of ligands and activation of transcription by nuclear receptors","volume":"30","author":"Steinmetz","year":"2001","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"2024091014261405200_CIT0066","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.immuni.2008.03.001","article-title":"Th17 cell differentiation: the long and winding road","volume":"28","author":"McGeachy","year":"2008","journal-title":"Immunity"},{"key":"2024091014261405200_CIT0067","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and Th17 Cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"2024091014261405200_CIT0068","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1178334","article-title":"Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells","volume":"327","author":"O\u2019Shea","year":"2010","journal-title":"Science"},{"key":"2024091014261405200_CIT0069","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.immuni.2014.04.004","article-title":"Small-molecule RORgammat antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms","volume":"40","author":"Xiao","year":"2014","journal-title":"Immunity"},{"key":"2024091014261405200_CIT0070","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.tips.2014.07.006","article-title":"Targeting Th17 cells in autoimmune diseases","volume":"35","author":"Yang","year":"2014","journal-title":"Trends Pharmacol Sci"},{"key":"2024091014261405200_CIT0071","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nature10075","article-title":"Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand","volume":"472","author":"Solt","year":"2011","journal-title":"Nature"},{"key":"2024091014261405200_CIT0072","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature09978","article-title":"Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgammat activity","volume":"472","author":"Huh","year":"2011","journal-title":"Nature"},{"key":"2024091014261405200_CIT0073","doi-asserted-by":"crossref","first-page":"22707","DOI":"10.1074\/jbc.C111.250407","article-title":"Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein","volume":"286","author":"Xu","year":"2011","journal-title":"J Biol Chem"},{"key":"2024091014261405200_CIT0074","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.cell.2015.11.009","article-title":"Single-cell genomics unveils critical regulators of Th17 cell pathogenicity","volume":"163","author":"Gaublomme","year":"2015","journal-title":"Cell"},{"key":"2024091014261405200_CIT0075","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.cell.2015.10.068","article-title":"CD5L\/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity","volume":"163","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"2024091014261405200_CIT0076","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cmet.2010.04.013","article-title":"Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity","volume":"11","author":"Kurokawa","year":"2010","journal-title":"Cell Metab"},{"key":"2024091014261405200_CIT0077","doi-asserted-by":"crossref","first-page":"5822","DOI":"10.1093\/emboj\/20.21.5822","article-title":"X-ray structure of the orphan nuclear receptor RORbeta ligand-binding domain in the active conformation","volume":"20","author":"Stehlin","year":"2001","journal-title":"EMBO J"},{"key":"2024091014261405200_CIT0078","doi-asserted-by":"crossref","first-page":"eadd4346","DOI":"10.1126\/sciimmunol.add4346","article-title":"1-Oleoyl-lysophosphatidylethanolamine stimulates ROR\u03b3t activity in T(H)17 cells","volume":"8","author":"Endo","year":"2023","journal-title":"Sci Immunol"},{"key":"2024091014261405200_CIT0079","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nchembio.1714","article-title":"Sterol metabolism controls T(H)17 differentiation by generating endogenous RORgamma agonists","volume":"11","author":"Hu","year":"2015","journal-title":"Nat Chem Biol"},{"key":"2024091014261405200_CIT0080","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cmet.2015.01.004","article-title":"Identification of natural RORgamma ligands that regulate the development of lymphoid cells","volume":"21","author":"Santori","year":"2015","journal-title":"Cell Metab"},{"key":"2024091014261405200_CIT0081","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/intimm\/dxp037","article-title":"Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3+ regulatory T cells","volume":"21","author":"Kagami","year":"2009","journal-title":"Int Immunol"},{"key":"2024091014261405200_CIT0082","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s12026-019-09089-5","article-title":"On the immunoregulatory role of statins in multiple sclerosis: the effects on Th17 cells","volume":"67","author":"Ntolkeras","year":"2019","journal-title":"Immunol Res"},{"key":"2024091014261405200_CIT0083","doi-asserted-by":"crossref","first-page":"12163","DOI":"10.1073\/pnas.1322807111","article-title":"Oxysterols are agonist ligands of RORgammat and drive Th17 cell differentiation","volume":"111","author":"Soroosh","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024091014261405200_CIT0084","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1038\/s41467-018-07203-z","article-title":"Sumoylation of ROR\u03b3t regulates T(H)17 differentiation and thymocyte development","volume":"9","author":"He","year":"2018","journal-title":"Nat Commun"},{"key":"2024091014261405200_CIT0085","doi-asserted-by":"crossref","first-page":"eadc9221","DOI":"10.1126\/sciadv.adc9221","article-title":"Decoupling the role of ROR\u03b3t in the differentiation and effector function of T(H)17 cells","volume":"8","author":"Zhong","year":"2022","journal-title":"Sci Adv"},{"key":"2024091014261405200_CIT0086","doi-asserted-by":"crossref","first-page":"eaat5401","DOI":"10.1126\/sciadv.aat5401","article-title":"GLK-IKK\u03b2 signaling induces dimerization and translocation of the AhR-ROR\u03b3t complex in IL-17A induction and autoimmune disease","volume":"4","author":"Chuang","year":"2018","journal-title":"Sci Adv"},{"key":"2024091014261405200_CIT0087","doi-asserted-by":"crossref","first-page":"110520","DOI":"10.1016\/j.celrep.2022.110520","article-title":"ROR\u03b3t phosphorylation protects against T cell-mediated inflammation","volume":"38","author":"Ma","year":"2022","journal-title":"Cell Rep"},{"key":"2024091014261405200_CIT0088","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/ni.3832","article-title":"A two-amino-acid substitution in the transcription factor ROR\u03b3t disrupts its function in T(H)17 differentiation but not in thymocyte development","volume":"18","author":"He","year":"2017","journal-title":"Nat Immunol"},{"key":"2024091014261405200_CIT0089","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.immuni.2015.09.007","article-title":"Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine","volume":"43","author":"Haghikia","year":"2015","journal-title":"Immunity"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/advance-article-pdf\/doi\/10.1093\/intimm\/dxae031\/58181880\/dxae031.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/36\/10\/487\/59074397\/dxae031.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/36\/10\/487\/59074397\/dxae031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T10:29:07Z","timestamp":1725964147000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/36\/10\/487\/7686464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,2]]},"references-count":89,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,6,2]]},"published-print":{"date-parts":[[2024,9,10]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxae031","relation":{},"ISSN":["1460-2377"],"issn-type":[{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10]]},"published":{"date-parts":[[2024,6,2]]}}}