Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene.

The Journal of Experimental Medicine
Masakatsu YamashitaToshinori Nakayama

Abstract

The maintenance of memory T cells is central to the establishment of immunological memory, although molecular details of the process are poorly understood. In the absence of the polycomb group (PcG) gene Bmi1, the number of memory CD4(+) T helper (Th)1/Th2 cells was reduced significantly. Enhanced cell death of Bmi1(-/-) memory Th2 cells was observed both in vivo and in vitro. Among various proapoptotic genes that are regulated by Bmi1, the expression of proapoptotic BH3-only protein Noxa was increased in Bmi1(-/-) effector Th1/Th2 cells. The generation of memory Th2 cells was restored by the deletion of Noxa, but not by Ink4a and Arf. Direct binding of Bmi1 to the Noxa gene locus was accompanied by histone H3-K27 methylation. The recruitment of other PcG gene products and Dnmt1 to the Noxa gene was highly dependent on the expression of Bmi1. In addition, Bmi1 was required for DNA CpG methylation of the Noxa gene. Moreover, memory Th2-dependent airway inflammation was attenuated substantially in the absence of Bmi1. Thus, Bmi1 controls memory CD4(+) Th1/Th2 cell survival and function through the direct repression of the Noxa gene.

References

Jan 1, 1995·Annual Review of Immunology·S L Reiner, R M Locksley
Jan 1, 1994·Annual Review of Immunology·R A Seder, W E Paul
May 23, 1998·Annual Review of Immunology·R W DuttonS L Swain
Sep 12, 1998·Journal of Virology·H MiyoshiI M Verma
Jun 23, 1999·Current Opinion in Genetics & Development·M van Lohuizen
Sep 29, 1999·Biochimica Et Biophysica Acta·D P Satijn, A P Otte
Feb 28, 2002·Annual Review of Immunology·Jonathan Sprent, Charles D Surh
May 11, 2002·Nature Reviews. Immunology·Susan M KaechRaft Ahmed
Sep 3, 2002·The Journal of Biological Chemistry·Masakatsu YamashitaToshinori Nakayama
Dec 4, 2002·Nature Reviews. Immunology·Antonio Lanzavecchia, Federica Sallusto
Dec 24, 2002·Nature Immunology·I-Hsin SuAlexander Tarakhovsky
Jan 4, 2003·The Journal of Clinical Investigation·Tohru KamataToshinori Nakayama
Feb 8, 2003·Current Opinion in Genetics & Development·Scott W Lowe, Charles J Sherr
Apr 2, 2003·Nature Reviews. Immunology·Kimberly S Schluns, Leo Lefrançois
Jun 17, 2003·Nature Immunology·Benedict SeddonRose Zamoyska
Dec 10, 2003·The Journal of Experimental Medicine·Robyn M KondrackLinda M Bradley
Dec 12, 2003·Nature·Joseph T OpfermanStanley J Korsmeyer
Dec 17, 2003·The Journal of Experimental Medicine·JiChu LiSusan L Swain
Mar 17, 2004·Current Opinion in Immunology·David MasopustRafi Ahmed
Mar 23, 2004·Annual Review of Immunology·Philippa Marrack, John Kappler
Jun 4, 2004·Molecular Cell·Liangjun WangRichard S Jones
Jul 20, 2004·The Journal of Biological Chemistry·Masakatsu YamashitaToshinori Nakayama
Sep 24, 2004·Nature·Hengbin WangYi Zhang
Feb 19, 2005·Science·Joseph T OpfermanStanley J Korsmeyer
Feb 19, 2005·Nature Reviews. Immunology·Andreas Strasser
Jun 21, 2005·Genes & Development·Sophia W M BruggemanMaarten van Lohuizen
Oct 26, 2005·Current Opinion in Cell Biology·Simon N Willis, Jerry M Adams

❮ Previous
Next ❯

Citations

Feb 2, 2012·Journal of Clinical Immunology·Li MaRenchi Yang
Jul 17, 2008·Immunologic Research·Timothy W Hand, Susan M Kaech
Jul 31, 2009·Oncogene·E Lomonosova, G Chinnadurai
Jul 31, 2009·Oncogene·C PlonerA Villunger
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Qiuyan WangYihong Ye
Jun 19, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jonathan G MoggsIan Kimber
Sep 3, 2010·PloS One·Matthew A SchallerSteven L Kunkel
Sep 2, 2010·Cell Stem Cell·Martin Sauvageau, Guy Sauvageau
Feb 14, 2016·International Immunology·Kiyoshi Hirahara, Toshinori Nakayama
Mar 5, 2016·Journal of Hematology & Oncology·Arnold BolomskyHeinz Ludwig
Jun 1, 2011·Journal of Molecular Signaling·Eyal JacobOrly Avni
May 24, 2016·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Jin KumagaiToshinori Nakayama
Dec 4, 2016·Annual Review of Immunology·Toshinori NakayamaYoshitaka Okamoto
Jun 29, 2017·Immunological Reviews·Damon J TumesToshinori Nakayama
Jul 4, 2017·Expert Opinion on Therapeutic Targets·Jeroen E GuikemaEric Eldering
Nov 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takeshi YamadaMasakatsu Yamashita
Jul 1, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Atsushi OnoderaToshinori Nakayama
Jan 18, 2014·Virology : Research and Treatment·Katarzyna KaczmarekAndrew J Henderson
Sep 30, 2017·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Masumeh Maleki BehzadNajmaldin Saki
Sep 27, 2018·Journal of Cellular and Molecular Medicine·Wei LiHaidan Liu
Feb 17, 2018·Clinical Epigenetics·Eric HervouetPierre-François Cartron
Jul 20, 2010·Immunological Reviews·K Kai McKinstrySusan L Swain
May 16, 2012·European Journal of Immunology·Masashi WatanabeRyo Abe
Aug 14, 2013·British Journal of Haematology·Christopher G J McKenzieJohn W Semple
Aug 16, 2014·Immunological Reviews·Rhys S Allan, Stephen L Nutt
Jul 20, 2018·Frontiers in Immunology·Matthew R Smith-RaskaBoris Reizis
Feb 26, 2015·Oncotarget·Violetta V LeshchenkoSamir Parekh

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
flow cytometry
immunoprecipitation
ChIP
PCR
acetylation
lavage
ELISA
ubiquitination
transfection

Related Concepts

Related Feeds