Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function

The Journal of Immunology : Official Journal of the American Association of Immunologists
Satoshi TanakaShimon Sakaguchi

Abstract

Mice with a mutation of the zeta-associated protein of 70 kDa gene (skg mutation) are genetically prone to develop autoimmune arthritis, depending on the environment. In a set of mice with the mutation, the amount of zeta-associated protein of 70 kDa protein as well as its tyrosine phosphorylation upon TCR stimulation decreased from +/+, skg/+, skg/skg, to skg/- mice in a stepwise manner. The reduction resulted in graded alterations of thymic positive and negative selection of self-reactive T cells and Foxp3(+) natural regulatory T cells (Tregs) and their respective functions. Consequently, skg/- mice spontaneously developed autoimmune arthritis even in a microbially clean environment, whereas skg/skg mice required stimulation through innate immunity for disease manifestation. After Treg depletion, organ-specific autoimmune diseases, especially autoimmune gastritis, predominantly developed in +/+, at a lesser incidence in skg/+, but not in skg/skg BALB/c mice, which suffered from other autoimmune diseases, especially autoimmune arthritis. In correlation with this change, gastritis-mediating TCR transgenic T cells were positively selected in +/+, less in skg/+, but not in skg/skg BALB/c mice. Similarly, on the genetic background...Continue Reading

References

Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·A C ChanA Weiss
Jan 1, 1991·Annual Review of Immunology·A HermanA M Pullen
Sep 1, 1993·The Journal of Experimental Medicine·P L PodolinL S Wicker
Feb 1, 1996·The Journal of Experimental Medicine·D QianA Weiss
Aug 1, 1996·The Journal of Experimental Medicine·M AsanoS Sakaguchi
May 1, 1999·Journal of Autoimmunity·H Braley-MullenH Tang
Jun 18, 2002·Science·Enrique AguadoMarie Malissen
Nov 5, 2002·Annual Review of Immunology·Timothy K StarrKristin A Hogquist
Jan 18, 2003·Science·Chandrashekhar Pasare, Ruslan Medzhitov
Mar 5, 2003·Immunological Reviews·Harald von BoehmerLudger Klein
Mar 22, 2003·Science·Guy WerlenEd Palmer
Oct 14, 2003·Trends in Immunology·Lisa A Pitcher, Nicolai S C van Oers
Mar 30, 2005·The Journal of Experimental Medicine·Connie L SommersLawrence E Samelson
Oct 6, 2005·The Journal of Experimental Medicine·Jason D FontenotAlexander Y Rudensky
Oct 11, 2005·Current Opinion in Immunology·Shimon Sakaguchi, Noriko Sakaguchi
Feb 8, 2006·The Journal of Biological Chemistry·Jiansheng WuJames M Clark
May 30, 2006·Seminars in Immunology·Peter K GregersenAnn B Begovich
Aug 15, 2006·Immunological Reviews·Shimon SakaguchiTakashi Nomura
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomoya KatakaiAkira Shimizu
Sep 5, 2007·The Journal of Allergy and Clinical Immunology·Thilo JakobHeinrich Flaswinkel
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eileen T SamyKenneth S K Tung
May 31, 2008·Cell·Shimon SakaguchiMasahiro Ono
Aug 20, 2008·International Immunology·Chiaki Wakasa-MorimotoShimon Sakaguchi
Jun 24, 2009·European Journal of Immunology·Capucine PicardClaire Hivroz

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Citations

Jan 10, 2012·Nature Medicine·Shimon SakaguchiRichard M Ransohoff
Sep 5, 2012·The Journal of Experimental Medicine·Sujin HwangPaul E Love
Jul 2, 2014·Nature Reviews. Rheumatology·Makoto MiyaraShimon Sakaguchi
Apr 9, 2014·The Journal of Experimental Medicine·Shivani SrivastavaDaniel J Campbell
Jan 20, 2016·The Journal of Experimental Medicine·Alice Y ChanJennifer M Puck
Dec 21, 2013·International Reviews of Immunology·Laura PasseriniRosa Bacchetta
Mar 8, 2018·International Journal of Molecular Sciences·Gap Ryol Lee
Dec 14, 2017·Annual Review of Immunology·Byron B Au-YeungArthur Weiss
Nov 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yelena BronevetskyJoseph M McCune
Oct 27, 2011·FEBS Letters·Shimon SakaguchiMotomu Hashimoto
Apr 26, 2011·FEBS Letters·Saba Alzabin, Richard O Williams
Mar 31, 2016·Nature Reviews. Immunology·Ming O Li, Alexander Y Rudensky
Apr 26, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takashi MatsuoTsuneyo Mimori
Feb 14, 2012·Arthritis and Rheumatism·Merja RuutuRanjeny Thomas
Apr 28, 2012·European Journal of Immunology·Arnaud DelpouxCédric Auffray
Feb 13, 2014·Immunological Reviews·Alexandria HuynhLaurence A Turka
Jan 17, 2020·Immunological Reviews·Yusuke TakeuchiShimon Sakaguchi
Jan 12, 2016·Current Opinion in Rheumatology·Emilie CoswayCatriona Prendergast
Mar 24, 2020·Journal of Leukocyte Biology·Mukul PrasadNicholas R J Gascoigne
Mar 16, 2012·Immunology and Cell Biology·Shimon SakaguchiRanjeny Thomas
Jan 28, 2015·Arthritis & Rheumatology·Athan C BailletRanjeny Thomas
Jul 16, 2016·Immunological Investigations·Maryam AzimiEisa Salehi
Feb 11, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Owen M SiggsChristopher C Goodnow
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyle Leonard O'HaganHyewon Phee
Sep 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Laura F SuMark M Davis
Mar 21, 2019·Seminars in Immunopathology·Keiko YasudaKeiji Hirota
Jun 27, 2019·Scientific Reports·Tania SinghIsabella Artner
Jan 21, 2020·Immunological Reviews·Charlie BridgewoodDennis McGonagle
Jan 21, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa K PetersonLeonard L Dragone
Aug 23, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·S Alice Long, Jane H Buckner
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Steven A SchaffertChang-Zheng Chen
Jun 12, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li-Tzu YehHuey-Kang Sytwu
Mar 27, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masatsugu Oh-HoraSho Yamasaki
Oct 22, 2011·European Journal of Immunology·James B Wing, Shimon Sakaguchi
Jun 12, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shatakshi SoodRose Zamoyska
Mar 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Olivia A PerngAndrew J Caton
Nov 7, 2017·Scandinavian Journal of Immunology·R EngelmannB Müller-Hilke
Feb 16, 2012·Pediatric Diabetes·Kristiina LuopajärviOuti Vaarala
Apr 28, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christian J MaineLinda A Sherman

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