Literature DB >> 28258823

Small-Molecule RORγt Antagonists: One Stone Kills Two Birds.

Chao Zhong1, Jinfang Zhu2.   

Abstract

Although small-molecule thymus-specific isoform of retinoic acid receptor-related orphan nuclear receptor γ (RORγt) antagonists suppressing interleukin (IL)-17-producing T helper (Th17) cells are widely reported, the effect of these molecules on other RORγt-expressing cells is unknown. However, a new study reports that RORγt inhibition in CD4+CD8+ thymocytes resulted in skewed T cell repertoire, contributing to a reduction in the frequency of self-reactive T cells and resistance to autoimmunity. Published by Elsevier Ltd.

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Year:  2017        PMID： 28258823      PMCID： PMC5378633          DOI： 10.1016/j.it.2017.02.006

Source DB:  PubMed          Journal:  Trends Immunol        ISSN： 1471-4906            Impact factor:   16.687


  10 in total

1.  Inhibition of RORγT Skews TCRα Gene Rearrangement and Limits T Cell Repertoire Diversity.

Authors:  Yanxia Guo; Kenzie D MacIsaac; Yi Chen; Richard J Miller; Renu Jain; Barbara Joyce-Shaikh; Heidi Ferguson; I-Ming Wang; Razvan Cristescu; John Mudgett; Laura Engstrom; Kyle J Piers; Gretchen A Baltus; Kenneth Barr; Hongjun Zhang; Huseyin Mehmet; Laxminarayan G Hegde; Xiao Hu; Laura L Carter; Thomas D Aicher; Gary Glick; Dennis Zaller; Abbas Hawwari; Craig C Correll; Dallas C Jones; Daniel J Cua
Journal:  Cell Rep       Date:  2016-12-20       Impact factor: 9.423

Review 2.  The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing.

Authors:  Sarah L Gaffen; Renu Jain; Abhishek V Garg; Daniel J Cua
Journal:  Nat Rev Immunol       Date:  2014-09       Impact factor: 53.106

3.  The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.

Authors:  Ivaylo I Ivanov; Brent S McKenzie; Liang Zhou; Carlos E Tadokoro; Alice Lepelley; Juan J Lafaille; Daniel J Cua; Dan R Littman
Journal:  Cell       Date:  2006-09-22       Impact factor: 41.582

4.  Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.

Authors:  Jian Guo; Abbas Hawwari; Hong Li; Zuoming Sun; Sanjeev K Mahanta; Dan R Littman; Michael S Krangel; You-Wen He
Journal:  Nat Immunol       Date:  2002-04-22       Impact factor: 25.606

Review 5.  REV-ERB and ROR nuclear receptors as drug targets.

Authors:  Douglas J Kojetin; Thomas P Burris
Journal:  Nat Rev Drug Discov       Date:  2014-03       Impact factor: 84.694

6.  Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms.

Authors:  Sheng Xiao; Nir Yosef; Jianfei Yang; Yonghui Wang; Ling Zhou; Chen Zhu; Chuan Wu; Erkan Baloglu; Darby Schmidt; Radha Ramesh; Mercedes Lobera; Mark S Sundrud; Pei-Yun Tsai; Zhijun Xiang; Jinsong Wang; Yan Xu; Xichen Lin; Karsten Kretschmer; Peter B Rahl; Richard A Young; Zhong Zhong; David A Hafler; Aviv Regev; Shomir Ghosh; Alexander Marson; Vijay K Kuchroo
Journal:  Immunity       Date:  2014-04-17       Impact factor: 31.745

7.  Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.

Authors:  Jun R Huh; Monica W L Leung; Pengxiang Huang; Daniel A Ryan; Michael R Krout; Raghu R V Malapaka; Jonathan Chow; Nicolas Manel; Maria Ciofani; Sangwon V Kim; Adolfo Cuesta; Fabio R Santori; Juan J Lafaille; H Eric Xu; David Y Gin; Fraydoon Rastinejad; Dan R Littman
Journal:  Nature       Date:  2011-03-27       Impact factor: 49.962

8.  Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.

Authors:  Laura A Solt; Naresh Kumar; Philippe Nuhant; Yongjun Wang; Janelle L Lauer; Jin Liu; Monica A Istrate; Theodore M Kamenecka; William R Roush; Dušica Vidović; Stephan C Schürer; Jihong Xu; Gail Wagoner; Paul D Drew; Patrick R Griffin; Thomas P Burris
Journal:  Nature       Date:  2011-04-17       Impact factor: 49.962

9.  Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells.

Authors:  David R Withers; Matthew R Hepworth; Xinxin Wang; Emma C Mackley; Emily E Halford; Emma E Dutton; Clare L Marriott; Verena Brucklacher-Waldert; Marc Veldhoen; Judith Kelsen; Robert N Baldassano; Gregory F Sonnenberg
Journal:  Nat Med       Date:  2016-02-15       Impact factor: 53.440

10.  Identification of an allosteric binding site for RORγt inhibition.

Authors:  Marcel Scheepstra; Seppe Leysen; Geert C van Almen; J Richard Miller; Jennifer Piesvaux; Victoria Kutilek; Hans van Eenennaam; Hongjun Zhang; Kenneth Barr; Sunil Nagpal; Stephen M Soisson; Maria Kornienko; Kristen Wiley; Nathaniel Elsen; Sujata Sharma; Craig C Correll; B Wesley Trotter; Mario van der Stelt; Arthur Oubrie; Christian Ottmann; Gopal Parthasarathy; Luc Brunsveld
Journal:  Nat Commun       Date:  2015-12-07       Impact factor: 14.919
  10 in total
  7 in total

1.  ROR(GMMA)T Modulating Activity for the Treatment of Cancers.

Authors:  Robert B Kargbo
Journal:  ACS Med Chem Lett       Date:  2018-05-22       Impact factor: 4.345

Review 2.  Emerging targets signaling for inflammation in Parkinson's disease drug discovery.

Authors:  Rhema Chandan Khairnar; Niraj Parihar; Kedar S Prabhavalkar; Lokesh Kumar Bhatt
Journal:  Metab Brain Dis       Date:  2022-05-10       Impact factor: 3.655

3.  lncRNA STAT4-AS1 Inhibited TH17 Cell Differentiation by Targeting RORγt Protein.

Authors:  Hanlin He; Xiangjie Qiu; Mingming Qi; Ousman Bajinka; Ling Qin; Yurong Tan
Journal:  J Immunol Res       Date:  2022-04-28       Impact factor: 4.493

Review 4.  Update on regulation and effector functions of Th17 cells.

Authors:  Ivy Sandquist; Jay Kolls
Journal:  F1000Res       Date:  2018-02-19

5.  RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients.

Authors:  Koen Venken; Peggy Jacques; Céline Mortier; Mark E Labadia; Tine Decruy; Julie Coudenys; Kathleen Hoyt; Anita L Wayne; Robert Hughes; Michael Turner; Sofie Van Gassen; Liesbet Martens; Dustin Smith; Christian Harcken; Joseph Wahle; Chao-Ting Wang; Eveline Verheugen; Nadia Schryvers; Gaëlle Varkas; Heleen Cypers; Ruth Wittoek; Yves Piette; Lieve Gyselbrecht; Serge Van Calenbergh; Filip Van den Bosch; Yvan Saeys; Gerald Nabozny; Dirk Elewaut
Journal:  Nat Commun       Date:  2019-01-02       Impact factor: 14.919

6.  Ligand-Based Design of Allosteric Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) Inverse Agonists.

Authors:  Femke A Meijer; Richard G Doveston; Rens M J M de Vries; Gaël M Vos; Alex A A Vos; Seppe Leysen; Marcel Scheepstra; Christian Ottmann; Lech-Gustav Milroy; Luc Brunsveld
Journal:  J Med Chem       Date:  2019-12-24       Impact factor: 7.446

7.  Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression.

Authors:  Abdulla Watad; Hannah Rowe; Charlie Bridgewood; Dennis G McGonagle; Tobias Russell; Qiao Zhou; Lisa K Anderson; Almas Khan; Robert Dunsmuir; Peter Loughenbury; Vishal Borse; Abhay Rao; Peter A Millner; Nicola Luigi Bragazzi; Howard Amital; Richard Cuhtbert; Miriam Wittmann; Kassem Sharif; Tony Kenna; Matthew A Brown; Darren Newton
Journal:  Ann Rheum Dis       Date:  2020-05-13       Impact factor: 27.973
  7 in total

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