Arginine deficiency leads to impaired cofilin dephosphorylation in activated human T lymphocytes

International Immunology
Nadja FeldmeyerMarkus Munder

Abstract

The amino acid arginine is fundamentally involved in the regulation of the immune response during infection, inflammatory diseases and tumor growth. Arginine deficiency (e.g. due to the myeloid cell enzyme arginase) inhibits proliferation and effector functions of activated T lymphocytes. Here, we studied intracellular mechanisms mediating this suppression of human T lymphocytes. Our proteomic analysis revealed an impaired dephosphorylation of the actin-binding protein cofilin upon T-cell activation in the absence of arginine. We show that this correlates with alteration of actin polymerization and impaired accumulation of CD2 and CD3 in the evolving immunological synapse in T cell-antigen presenting cells conjugates. In contrast, T-cell cytokine synthesis is differentially regulated in human T lymphocytes in the absence of arginine. While the production of certain cytokines (e.g. IFN-γ) is severely reduced, T lymphocytes produce other cytokines (e.g. IL-2) independent of extracellular arginine. MEK and PI3K activity are reciprocally regulated in association with impaired cofilin dephosphorylation. Finally, we show that impaired cofilin dephosphorylation is also detectable in human T cells activated in a granulocyte-dominated p...Continue Reading

References

May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y SamstagS C Meuer
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·C WülfingM M Davis
Jun 20, 2001·Trends in Cell Biology·J Condeelis
Apr 16, 2002·The Journal of Biological Chemistry·Paulo C RodriguezAugusto C Ochoa
Dec 20, 2002·Nature·Carl Nathan
Jan 15, 2003·Journal of Leukocyte Biology·Yvonne SamstagGuido H Wabnitz
Jun 18, 2003·Trends in Immunology·Vincenzo BrontePaola Zanovello
Feb 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sybille M EibertYvonne Samstag
May 20, 2006·Blood·Markus MunderAnthony D Ho
Aug 18, 2006·Nature Reviews. Cancer·David M Sabatini
Oct 7, 2006·Blood·Paulo C RodriguezAugusto C Ochoa
Mar 3, 2007·European Journal of Immunology·Pascale KropfIngrid Müller
Feb 29, 2008·Annual Review of Immunology·Janis K BurkhardtMeredith H Shaffer
Feb 7, 2009·Nature Reviews. Immunology·Dmitry I Gabrilovich, Srinivas Nagaraj
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johanna OberliesMarkus Munder
Jul 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Stephen P CobboldHerman Waldmann
Jul 29, 2009·European Journal of Immunology·Markus MunderPascale Kropf
Sep 22, 2009·British Journal of Pharmacology·Markus Munder
Dec 9, 2009·Annual Review of Immunology·David R FooksmanMichael L Dustin
Jun 18, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erikka L CarrKenneth A Frauwirth
Jul 20, 2010·Immunological Reviews·Ursula Grohmann, Vincenzo Bronte
Aug 13, 2010·Cold Spring Harbor Perspectives in Biology·Peter Beemiller, Matthew F Krummel
Oct 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paulo C RodriguezAugusto C Ochoa
Nov 30, 2010·Immunology Letters·Sabrina HoffmannGünter J Hämmerling

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Citations

Feb 21, 2013·Cellular and Molecular Life Sciences : CMLS·Janesh PillayLeo Koenderman
Feb 24, 2015·Nutrients·Karolina A P WijnandsMartijn Poeze
Oct 15, 2013·Immunological Reviews·Yvonne SamstagGuido H Wabnitz
Jul 21, 2015·Life Sciences·Michaela Pekarova, Antonin Lojek
Aug 26, 2016·Immunological Reviews·Louise W TreffersHanke L Matlung
Sep 23, 2016·PLoS Biology·Stephanie RossnaglInaam A Nakchbandi
May 1, 2018·Expert Review of Molecular Diagnostics·Alessandra RomanoFrancesco Di Raimondo
Aug 12, 2014·Journal of Leukocyte Biology·Katharina KappMarkus Munder
Jun 30, 2018·European Journal of Clinical Investigation·Cathelijn E M Aarts, Taco W Kuijpers
Apr 10, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zoltan V VargaPal Pacher
Apr 16, 2019·Mediators of Inflammation·Danielle MinnsEmily Gwyer Findlay
Jun 6, 2020·Frontiers in Immunology·Tomasz M GrzywaJakub Golab
Mar 27, 2018·Bulletin of Experimental Biology and Medicine·A N KazimirskiiL Yu Semenova
Sep 29, 2020·Frontiers in Immunology·Charita FurumayaHanke L Matlung
Oct 7, 2015·Frontiers in Immunology·Pieter H C LeliefeldJanesh Pillay
Jul 19, 2017·Trends in Cancer·Evgeniy B EruslanovSteven M Albelda
May 27, 2021·Cellular and Molecular Life Sciences : CMLS·Adrià-Arnau Martí I Líndez, Walter Reith
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Tao Du, Junyi Han
Jun 26, 2021·Pharmacology & Therapeutics·Tomasz M GrzywaJakub Golab
Aug 20, 2021·Clinical Medicine Insights. Oncology·Tianhang LiRong Yang

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