Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments.

Proceedings of the National Academy of Sciences of the United States of America
Dorothea BusseThomas Höfer

Abstract

Cytokines are pleiotropic and readily diffusible messenger molecules, raising the question of how their action can be confined to specific target cells. The T cell cytokine interleukin-2 (IL-2) is essential for the homeostasis of regulatory T (Treg) cells that suppress (auto)immunity and stimulates immune responses mediated by conventional T cells. We combined mathematical modeling and experiments to dissect the dynamics of the IL-2 signaling network that links the prototypical IL-2 producers, conventional T helper (Th) cells, and Treg cells. We show how the IL-2-induced upregulation of high-affinity IL-2 receptors (IL-2R) establishes a positive feedback loop of IL-2 signaling. This feedback mediates a digital switch for the proliferation of Th cells and functions as an analog amplifier for the IL-2 uptake capacity of Treg cells. Unlike other positive feedbacks in cell signaling that augment signal propagation, the IL-2/IL-2R loop enhances the capture of the signal molecule and its degradation. Thus Treg and Th cells can compete for IL-2 and restrict its range of action through efficient cellular uptake. Depending on activation status and spatial localization of the cells, IL-2 may be consumed exclusively by Treg or Th cells, o...Continue Reading

References

Jun 22, 1984·Science·D A Cantrell, K A Smith
Apr 9, 1993·Cell·T Taniguchi, Y Minami
Jun 3, 2000·Annual Review of Immunology·E M Shevach
Feb 16, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·David E LevyArun Prakash
Dec 14, 2002·Trends in Cell Biology·H Steven WileyDouglas A Lauffenburger
Jul 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ludger KleinHarald von Boehmer
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Warren N D'Souza, Leo Lefrançois
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hans DoomsAbul K Abbas
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dorothy K SojkaNevil J Singh
Jul 21, 2004·Progress in Biophysics and Molecular Biology·Luca MarianiThomas Höfer
Aug 13, 2004·European Journal of Immunology·Maurus de la RosaAlexander Scheffold
Apr 14, 2005·European Journal of Immunology·Alexander ScheffoldThomas Höfer
Oct 20, 2005·PLoS Biology·Grégoire Altan-Bonnet, Ronald N Germain
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dorothy K SojkaDeborah J Fowell
Feb 7, 2006·Trends in Immunology·Zoltán FehérvariShimon Sakaguchi
Feb 10, 2006·Cell Research·Kendall A Smith
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Afonso R M AlmeidaAntonio A Freitas
Jan 17, 2007·Expert Opinion on Biological Therapy·Onur BoymanJonathan Sprent
Mar 23, 2007·Nature·Masahiro OnoShimon Sakaguchi
Aug 1, 2007·The Journal of Experimental Medicine·Jae-Ho ChoJonathan Sprent
Sep 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nina OberleElisabeth Suri-Payer
Nov 21, 2007·Nature Immunology·Alexander ScheffoldThomas Höfer
Dec 8, 2007·Annual Review of Immunology·Thomas R Malek
May 22, 2008·European Journal of Immunology·Susan BrandenburgAlexander Scheffold
May 31, 2008·Cell·Shimon SakaguchiMasahiro Ono
Sep 19, 2008·Nature Immunology·Morgan HuseMark M Davis
Jun 3, 2009·Genes & Development·Li-Fan Lu, Alexander Rudensky

❮ Previous
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Citations

Jan 31, 2013·Bulletin of Mathematical Biology·Luis Mendoza
Oct 6, 2010·Theory in Biosciences = Theorie in Den Biowissenschaften·Luis Mendoza, Fátima Pardo
Feb 4, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Demelza J IrelandManfred W Beilharz
Jun 1, 1990·Biochimica Et Biophysica Acta·C H Blood, B R Zetter
Aug 9, 2012·Nature Communications·M G de Goër de HerveY Taoufik
Jan 15, 2013·Pediatric Research·Alexandra SittkaBernd T Schmeck
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qing HanJ Christopher Love
May 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yuval HartUri Alon
Jan 12, 2011·Annual Review of Immunology·Ronald N GermainIain D C Fraser
Sep 18, 2012·American Journal of Respiratory Cell and Molecular Biology·Milena J TosiekDunja Bruder
Mar 24, 2012·Blood·Kesley AttridgeLucy S K Walker
Aug 11, 2011·PLoS Computational Biology·Tilo BeyerJonathan A Lindquist
May 23, 2013·PLoS Pathogens·Iwana SchmitzManfred Kopf
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Thomas Charles ButlerArup K Chakraborty
Aug 19, 2014·Nature Reviews. Immunology·Georg Gasteiger, Alexander Y Rudensky
Dec 15, 2015·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Anna M BogdaliObtulowicz Krystyna
Apr 14, 2011·Molecular Systems Biology·Joao B Xavier
Apr 15, 2011·Immunological Reviews·Guoyan ChengThomas R Malek
Apr 10, 2014·Immunological Reviews·Markus Kleinewietfeld, David A Hafler
Feb 9, 2016·Immunology·Ana Sofia Figueiredo, Anne Schumacher
Oct 22, 2014·European Journal of Immunology·Pedro Milanez-AlmeidaJochen Huehn
Aug 15, 2015·Journal of Theoretical Biology·Majid Jaberi-DourakiAnmar Khadra
Feb 22, 2014·Immunopharmacology and Immunotoxicology·Sufia Butt HassanAnders Elm Pedersen
May 26, 2015·Cell Reports·Guillaume VoisinneGrégoire Altan-Bonnet
Apr 19, 2016·Immunological Reviews·Georg GasteigerWolfgang Kastenmüller
Jun 8, 2013·Bio Systems·Pablo Martínez-Sosa, Luis Mendoza

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