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The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration

Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation a...

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Autores principales: Collenburg, Lena, Beyersdorf, Niklas, Wiese, Teresa, Arenz, Christoph, Saied, Essa M., Becker-Flegler, Katrin Anne, Schneider-Schaulies, Sibylle, Avota, Elita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566967/
https://www.ncbi.nlm.nih.gov/pubmed/28871263
http://dx.doi.org/10.3389/fimmu.2017.01007
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author Collenburg, Lena
Beyersdorf, Niklas
Wiese, Teresa
Arenz, Christoph
Saied, Essa M.
Becker-Flegler, Katrin Anne
Schneider-Schaulies, Sibylle
Avota, Elita
author_facet Collenburg, Lena
Beyersdorf, Niklas
Wiese, Teresa
Arenz, Christoph
Saied, Essa M.
Becker-Flegler, Katrin Anne
Schneider-Schaulies, Sibylle
Avota, Elita
author_sort Collenburg, Lena
collection PubMed
description Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.
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spelling pubmed-55669672017-09-04 The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration Collenburg, Lena Beyersdorf, Niklas Wiese, Teresa Arenz, Christoph Saied, Essa M. Becker-Flegler, Katrin Anne Schneider-Schaulies, Sibylle Avota, Elita Front Immunol Immunology Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton. Frontiers Media S.A. 2017-08-21 /pmc/articles/PMC5566967/ /pubmed/28871263 http://dx.doi.org/10.3389/fimmu.2017.01007 Text en Copyright © 2017 Collenburg, Beyersdorf, Wiese, Arenz, Saied, Becker-Flegler, Schneider-Schaulies and Avota. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Collenburg, Lena
Beyersdorf, Niklas
Wiese, Teresa
Arenz, Christoph
Saied, Essa M.
Becker-Flegler, Katrin Anne
Schneider-Schaulies, Sibylle
Avota, Elita
The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration
title The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration
title_full The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration
title_fullStr The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration
title_full_unstemmed The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration
title_short The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration
title_sort activity of the neutral sphingomyelinase is important in t cell recruitment and directional migration
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566967/
https://www.ncbi.nlm.nih.gov/pubmed/28871263
http://dx.doi.org/10.3389/fimmu.2017.01007
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