Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sabine RingKarsten Mahnke

Abstract

Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC. We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4(+) T cells and form DC-Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4(+) T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC-Treg clusters, indicating a role for adenosine in guiding DC-Treg interactions. Analysis of the signal transduction events in DC after contact to Treg revealed increased levels of cAMP, followed by activation of Epac1 and the GTPase Rap1. Subsequently activated Rap1 localized to the subcortical actin cytoskeleton in DC, providing a means by which directed locomotion of DC toward Treg is facilitated. In aggregate, these data show that Treg degrade ATP to adenosine via CD39, attracting DC by activating Epac1-Rap1-dependent pathways. As a consequence, DC-Treg clusters are formed ...Continue Reading

References

Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·L M Williams, A J Ridley
Sep 5, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E PantherJ Norgauer
Oct 23, 2004·The Journal of Biological Chemistry·Huie JingDoina Ganea
Aug 31, 2006·Journal of Leukocyte Biology·Magdalena J LorenowiczMar Fernandez-Borja
Nov 7, 2006·Trends in Biochemical Sciences·Johannes L Bos
Dec 16, 2006·Science·Yu ChenWolfgang G Junger
May 16, 2007·The Journal of Experimental Medicine·Tobias BoppEdgar Schmitt
May 16, 2007·The Journal of Experimental Medicine·Silvia DeaglioSimon C Robson
Aug 3, 2007·Journal of Cancer Research and Clinical Oncology·Li WangPing Zhou
Dec 12, 2007·Angiogenesis·Evgenia V GerasimovskayaKurt R Stenmark
Jul 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yasushi OnishiShimon Sakaguchi
May 12, 2009·Trends in Immunology·György HaskóPál Pacher
May 12, 2009·The Journal of Allergy and Clinical Immunology·Sabine RingKarsten Mahnke
Jan 30, 2010·The Journal of Allergy and Clinical Immunology·Sabine RingKarsten Mahnke
Mar 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabine RingKarsten Mahnke
Mar 16, 2011·Cellular Signalling·Magali BrecklerFrank Lezoualc'h
Jul 20, 2011·European Journal of Immunology·Frederico S RegateiroHerman Waldmann
May 18, 2013·Nature Reviews. Immunology·Shimon SakaguchiHerman Waldmann

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Citations

Mar 18, 2016·Cancer Immunology, Immunotherapy : CII·Jinbao ZongMichael R Shurin
Aug 26, 2016·Purinergic Signalling·Martha de Oliveira BravoFelipe Saldanha-Araujo
Nov 29, 2016·Nature Reviews. Immunology·Tim WorbsReinhold Förster
Mar 5, 2017·Immunological Reviews·Bertrand AllardJohn Stagg
Mar 15, 2018·Physiological Reviews·William G Robichaux, Xiaodong Cheng
Mar 23, 2018·Cellular & Molecular Immunology·Laura TiberioSilvano Sozzani
Jan 30, 2019·International Journal of Molecular Sciences·Marta VuerichMaria Serena Longhi
Mar 1, 2016·Nature Reviews. Immunology·Caglar Cekic, Joel Linden
Jul 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tae-Sik NamUh-Hyun Kim
Dec 6, 2018·International Journal of Molecular Sciences·Kevin SekPaul A Beavis
Oct 1, 2020·Journal of Cancer Research and Clinical Oncology·Fei PengYu Hu
Dec 7, 2016·Seminars in Immunopathology·Lucía MinarrietaLuciana Berod
Nov 27, 2018·Frontiers in Immunology·Cinthia Silva-VilchesKarsten Mahnke
Oct 31, 2020·Frontiers in Pharmacology·Hannah K DrescherRalf Weiskirchen
Jun 12, 2021·Experimental Neurology·Yejun WuChunhua Chen
Jul 16, 2021·Life Sciences·Elham BaghbaniBehzad Baradaran

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