Epigenetic regulation of the expression of Il12 and Il23 and autoimmune inflammation by the deubiquitinase Trabid

Nature Immunology
Jin JinShao-Cong Sun

Abstract

The proinflammatory cytokines interleukin 12 (IL-12) and IL-23 connect innate responses and adaptive immune responses and are also involved in autoimmune and inflammatory diseases. Here we describe an epigenetic mechanism for regulation of the genes encoding IL-12 (Il12a and Il12b; collectively called 'Il12' here) and IL-23 (Il23a and Il12b; collectively called 'Il23' here) involving the deubiquitinase Trabid. Deletion of Zranb1 (which encodes Trabid) in dendritic cells inhibited induction of the expression of Il12 and Il23 by Toll-like receptors (TLRs), which impaired the differentiation of inflammatory T cells and protected mice from autoimmune inflammation. Trabid facilitated TLR-induced histone modifications at the promoters of Il12 and Il23, which involved deubiqutination and stabilization of the histone demethylase Jmjd2d. Our findings highlight an epigenetic mechanism for the regulation of Il12 and Il23 and establish Trabid as an innate immunological regulator of inflammatory T cell responses.

References

Nov 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·S SanjabiS T Smale
Jul 21, 2001·The Biochemical Journal·P C EvansP J Kilshaw
Aug 18, 2001·Cell·A Lanzavecchia, F Sallusto
Dec 25, 2002·Current Biology : CB·Andrew W SnowdenCarl O Pabo
Feb 4, 2003·Nature Reviews. Immunology·Giorgio Trinchieri
Mar 22, 2003·Current Opinion in Cell Biology·Wolfgang FischleC David Allis
Nov 18, 2004·Immunological Reviews·Claire L LangrishDaniel J Cua
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leesun KimEric Y Denkers
May 5, 2005·Molecular and Cellular Biology·William ReileyShao-Cong Sun
Sep 17, 2005·Genes & Development·Shomyseh SanjabiStephen T Smale
Jan 2, 2007·Journal of Neuroimmunology·Lisa K Peterson, Robert S Fujinami
Jan 24, 2007·Molecular and Cellular Biology·Liang ZhouStephen T Smale
Apr 5, 2007·Nature Protocols·Joel D NelsonKarol Bomsztyk
Jul 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jian XuStephen T Smale
Nov 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Setsuko Mise-OmataTakahiro S Doi
Mar 25, 2009·Nature Reviews. Genetics·Howard Cedar, Yehudit Bergman
Jan 16, 2010·Science·Akiko Iwasaki, Ruslan Medzhitov
Aug 31, 2010·Nature Chemical Biology·Satpal VirdeeJason W Chin
Feb 16, 2011·Cell Research·Andrew J Bannister, Tony Kouzarides
Apr 16, 2011·Trends in Immunology·Jarod ZeppXiaoxia Li
Dec 14, 2011·Nature Structural & Molecular Biology·Julien D F LicchesiDavid Komander
May 29, 2012·Molecular Cell·Yina ZhuSimona Saccani
Dec 6, 2012·Archives of Pharmacal Research·Young-Chang ChoBok Yun Kang
Jul 6, 2013·Nature Reviews. Immunology·Dipyaman GangulyBoris Reizis
Aug 26, 2014·Nature Reviews. Immunology·Sarah L GaffenDaniel J Cua
Aug 26, 2014·Cell Death and Differentiation·S R MihalyS Morioka

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Citations

Mar 26, 2016·Cell Research·Kirby N Swatek, David Komander
Mar 26, 2016·Cell Research·Hongbo Hu, Shao-Cong Sun
Dec 2, 2014·Pharmacology & Therapeutics·Katja SchmitzIrmgard Tegeder
Oct 8, 2013·Free Radical Biology & Medicine·Md Jamal UddinHun Taeg Chung
Jul 6, 2013·Human Immunology·Seema ChughAlpana Sharma
Jul 20, 2017·Nature Immunology·Inna S AfoninaRudi Beyaert
Feb 18, 2016·Nature Immunology·Inna S Afonina, Rudi Beyaert
Sep 30, 2017·Nature Reviews. Drug Discovery·Jeanine A HarriganStephen P Jackson
Jul 29, 2018·Frontiers of Medicine·Xiao-Dong Yang, Shao-Cong Sun
Oct 21, 2016·Nature·Tycho E T MevissenDavid Komander
Sep 15, 2017·Nature Reviews. Rheumatology·Esteban Ballestar, Tianlu Li
Jun 13, 2019·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Alberta L WangKelan G Tantisira
Apr 7, 2020·Journal of Neuroinflammation·Jing RuanXu Wang
Apr 27, 2016·Current Opinion in Clinical Nutrition and Metabolic Care·Dashzeveg Bayarsaihan
Jun 20, 2019·Frontiers in Immunology·Giselle M BoukhaledConnie M Krawczyk
Jul 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jia XuXuetao Cao
Jan 10, 2019·Cell & Bioscience·Xiaoping XieShao-Cong Sun
Nov 28, 2018·Nature Reviews. Gastroenterology & Hepatology·Alexander R MoschenTim Raine
Dec 31, 2019·Frontiers of Medicine·Jiansen DuLingqiang Zhang
Jan 14, 2021·Signal Transduction and Targeted Therapy·Xiaofei Zhou, Shao-Cong Sun
Jan 1, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Aug 27, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Ji ChengWenyi Wei
Jan 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Virginia De CesareSatpal Virdee
Jan 12, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Dec 29, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Leonard A JasonBen Z Katz
Aug 4, 2020·Neurobiology of Learning and Memory·Madeline MusausTimothy J Jarome
Apr 4, 2021·Microorganisms·Vera VozandychovaJiri Stulik
Apr 16, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Apr 17, 2021·Frontiers in Immunology·Ken MaesKarine Breckpot
May 1, 2021·International Journal of Molecular Sciences·Sander BekeschusRamona Clemen
May 30, 2019·Immunology Letters·Kazuyo YamamotoNorimitsu Kadowaki

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Methods Mentioned

BETA
ELISA
nuclear translocation
immunoprecipitation
ubiquitination
ChIP
deubiquitination
Knockout
flow cytometry
PCR
PMA

Software Mentioned

Trabid

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