Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease

Cell
Chiao-Wen YangAndrew C Chan

Abstract

The DENN domain is an evolutionary conserved protein module found in all eukaryotes and serves as an exchange factor for Rab-GTPases to regulate diverse cellular functions. Variants in DENND1B are associated with development of childhood asthma and other immune disorders. To understand how DENND1B may contribute to human disease, Dennd1b(-/-) mice were generated and exhibit hyper-allergic responses following antigen challenge. Dennd1b(-/-) TH2, but not other TH cells, exhibit delayed receptor-induced T cell receptor (TCR) downmodulation, enhanced TCR signaling, and increased production of effector cytokines. As DENND1B interacts with AP-2 and Rab35, TH2 cells deficient in AP-2 or Rab35 also exhibit enhanced TCR-mediated effector functions. Moreover, human TH2 cells carrying asthma-associated DENND1B variants express less DENND1B and phenocopy Dennd1b(-/-) TH2 cells. These results provide a molecular basis for how DENND1B, a previously unrecognized regulator of TCR downmodulation in TH2 cells, contributes to asthma pathogenesis and how DENN-domain-containing proteins may contribute to other human disorders.

References

Jul 1, 1987·European Journal of Immunology·A TelermanR Mosselmans
Sep 1, 1996·European Journal of Immunology·S ValituttiA Lanzavecchia
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·M NaramuraH Gu
Dec 2, 2000·Critical Reviews in Immunology·A Alcover, B Alarcón
Sep 21, 2001·Biochemical and Biophysical Research Communications·E LevivierI Callebaut
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Mar 5, 2004·Critical Reviews in Immunology·Carsten Geisler
Mar 23, 2006·Annual Review of Immunology·K Mark AnselAnjana Rao
Sep 5, 2006·Current Biology : CB·Ilektra KourantiArnaud Echard
Dec 22, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Patrick D AllairePeter S McPherson
May 3, 2008·The Journal of Biological Chemistry·Genaro Patino-LopezStephen Shaw
Nov 17, 2009·Immunological Reviews·Lakshmi BalagopalanLawrence E Samelson
Dec 25, 2009·The New England Journal of Medicine·Patrick M A SleimanHakon Hakonarson
Feb 16, 2010·The Journal of Biological Chemistry·Andrea L Marat, Peter S McPherson
Mar 20, 2010·American Journal of Respiratory and Critical Care Medicine·Bo L K ChawesHans Bisgaard
May 18, 2010·The Journal of Biological Chemistry·David A KorasickAntje Heese
Jul 20, 2010·Nature Genetics·Xiangdong LiuMichael F Seldin
Sep 24, 2010·The New England Journal of Medicine·Miriam F MoffattUNKNOWN GABRIEL Consortium
Oct 13, 2010·The Journal of Cell Biology·Shin-ichiro YoshimuraFrancis A Barr
Dec 15, 2010·European Journal of Human Genetics : EJHG·Manuel A R FerreiraNicholas G Martin
Feb 19, 2011·The Journal of Biological Chemistry·Andrea L MaratPeter S McPherson
Nov 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xudong WuKarin M Reinisch
Nov 11, 2011·Molecular Biology of the Cell·Andrea L MaratPeter S McPherson
Jan 26, 2012·Nature Reviews. Immunology·Gabrielle T Belz, Stephen L Nutt
Jul 27, 2012·Annual Review of Cell and Developmental Biology·Frances M Brodsky
Sep 11, 2012·Nature Genetics·Jimmy Z LiuUNKNOWN Wellcome Trust Case Control Consortium 3
Mar 26, 2013·Nature Reviews. Immunology·Rebecca J Brownlie, Rose Zamoyska
Apr 10, 2014·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·N L D SmithP Bowyer
Sep 5, 2015·Science·Douglas B WheelerCharles L Sawyers

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Citations

Jan 16, 2016·Cell·Marie Godar, Bart N Lambrecht
Jun 5, 2016·Journal of Molecular Biology·R Christopher D FurnissAbigail Clements
Mar 3, 2017·The Journal of Biological Chemistry·Jie Xu, Peter S McPherson
Oct 17, 2017·Bioinformatics·Sylvain PouxThe UniProt Consortium
Jan 27, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katarzyna BulekXiaoxia Li
Jan 26, 2016·Nature Reviews. Immunology·Yvonne Bordon
Oct 31, 2017·Nature Reviews. Immunology·Jennifer A Walker, Andrew N J McKenzie
Oct 15, 2019·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·David L DuffyNoe Zamel
Jun 21, 2019·Scientific Reports·Daniel Crespo-PiazueloJosep M Folch
Aug 23, 2019·EMBO Reports·Stefanie KuhnsOliver E Blacque
Dec 31, 2016·Food Science and Biotechnology·Tae-Gyu LimYoung Kyoung Rhee
Jan 10, 2018·Traffic·Ronan Shaughnessy, Arnaud Echard
Aug 14, 2019·Immunological Reviews·Loredana SaveanuClaire Hivroz
Feb 2, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Minghua ZhuWeiguo Zhang
Jun 2, 2016·Cell Structure and Function·Morié IshidaMitsunori Fukuda
Nov 3, 2020·Histochemistry and Cell Biology·Eugene Won ParkNobukazu Araki
Dec 31, 2020·International Journal of Molecular Sciences·Demetra S M ChatzileontiadouEmma J Grant
Jul 3, 2017·Molecular Immunology·Bianca S D FiuzaCamila A Figueiredo

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