(Inverse) Agonists of Retinoic Acid-Related Orphan Receptor γ: Regulation of Immune Responses, Inflammation, and Autoimmune Disease

Annual Review of Pharmacology and Toxicology
Anton M Jetten, Donald N Cook

Abstract

Retinoic acid-related orphan receptor γt (RORγt) functions as a ligand-dependent transcription factor that regulates multiple proinflammatory genes and plays a critical role in several inflammatory and autoimmune diseases. Various endogenous and synthetic RORγ (inverse) agonists have been identified that regulate RORγ transcriptional activity, including many cholesterol intermediates and oxysterols. Changes in cholesterol biosynthesis and metabolism can therefore have a significant impact on the generation of oxysterol RORγ ligands and, consequently, can control RORγt activity and inflammation. These observations contribute to a growing literature that connects cholesterol metabolism to the regulation of immune responses and autoimmune disease. Loss of RORγ function in knockout mice and in mice treated with RORγ inverse agonists results in reduced production of proinflammatory cytokines, such as IL-17A/F, and increased resistance to autoimmune disease in several experimental rodent models. Thus, RORγt inverse agonists might provide an attractive therapeutic approach to treat a variety of autoimmune diseases.

References

Dec 30, 1994·Biochemical and Biophysical Research Communications·T HiroseA M Jetten
Aug 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·S KurebayashiA M Jetten
Jan 15, 2004·The Journal of Biological Chemistry·Joerg KallenBrigitte Fournier
Feb 6, 2007·The Journal of Biological Chemistry·Xuexian O YangChen Dong
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen L TilleyAnton M Jetten
Aug 7, 2007·Nature Immunology·Anne BrüstleMichael Lohoff
Dec 7, 2007·Seminars in Immunology·Ivaylo I IvanovDan R Littman
Apr 25, 2008·The Journal of Biological Chemistry·Kenji IchiyamaTakashi Kobayashi
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xin ZhangSilva Markovic-Plese
Nov 20, 2008·The British Journal of Dermatology·C JohansenK Kragballe
Dec 2, 2008·Biochemical and Biophysical Research Communications·Eun Ju HwangKeun Il Kim
Mar 6, 2009·International Immunology·Amit Awasthi, Vijay K Kuchroo
Jul 7, 2009·Nature·Barbara U SchramlKenneth M Murphy
Jun 19, 2010·Nature Reviews. Immunology·Daniel J Cua, Cristina M Tato
Oct 12, 2010·Science·Shinichiro SawaGérard Eberl
Oct 22, 2010·Nature·Kamran GhoreschiJohn J O'Shea
Apr 26, 2011·Biochemical and Biophysical Research Communications·Michael ErmischDieter Steinhilber
May 18, 2011·The Journal of Experimental Medicine·Alessandra GeremiaFiona Powrie
Sep 7, 2011·Journal of Innate Immunity·Patricia Aparicio-Domingo, Tom Cupedo

❮ Previous
Next ❯

Citations

Aug 14, 2020·American Journal of Physiology. Endocrinology and Metabolism·Andrzej T SlominskiChander Raman
Sep 11, 2020·Cells·Gloria Pastor-FernándezMaría N Navarro
Aug 12, 2020·Experimental Dermatology·Radomir M SlominskiAndrzej T Slominski
Oct 30, 2020·Natural Product Reports·Angela LadurnerVerena M Dirsch
May 28, 2021·Scientific Reports·Xiaohua XueRobin L Thurmond
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haozhen MaFang Huang
Jun 20, 2020·ACS Medicinal Chemistry Letters·Robert J CherneyT G Murali Dhar
Aug 28, 2021·International Journal of Molecular Sciences·Georgeta BochevaAndrzej T Slominski
Sep 22, 2021·Journal of Molecular Biology·Timothy S StrutzenbergPatrick R Griffin
Aug 1, 2020·The American Journal of Pathology·Michel E MickaelRajatava Basu

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
ubiquitination
deubiquitination
sumoylation
X-ray

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.