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The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling

Splenic marginal zone B cells (MZB) shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery. However, it is unclear how MZBs migrate directionally from the marginal zone to the follicle. Here, we show that murine MZBs migrate up shear flow via the...

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Autores principales: Tedford, Kerry, Steiner, Michael, Koshutin, Stanislav, Richter, Karin, Tech, Laura, Eggers, Yannik, Jansing, Inga, Schilling, Kerstin, Hauser, Anja Erika, Korthals, Mark, Fischer, Klaus-Dieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741619/
https://www.ncbi.nlm.nih.gov/pubmed/29273735
http://dx.doi.org/10.1038/s41467-017-02482-4
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author Tedford, Kerry
Steiner, Michael
Koshutin, Stanislav
Richter, Karin
Tech, Laura
Eggers, Yannik
Jansing, Inga
Schilling, Kerstin
Hauser, Anja Erika
Korthals, Mark
Fischer, Klaus-Dieter
author_facet Tedford, Kerry
Steiner, Michael
Koshutin, Stanislav
Richter, Karin
Tech, Laura
Eggers, Yannik
Jansing, Inga
Schilling, Kerstin
Hauser, Anja Erika
Korthals, Mark
Fischer, Klaus-Dieter
author_sort Tedford, Kerry
collection PubMed
description Splenic marginal zone B cells (MZB) shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery. However, it is unclear how MZBs migrate directionally from the marginal zone to the follicle. Here, we show that murine MZBs migrate up shear flow via the LFA-1 (αLβ2) integrin ligand ICAM-1, but adhere or migrate down the flow via the VLA-4 integrin (α4β1) ligand VCAM-1. MZBs lacking Arhgef6 (Pak-interacting exchange factor (αPIX)) or functional LFA-1 are impaired in shuttling due to mislocalization toward the VCAM-1-rich red pulp. Sphingosine-1-phosphate (S1P) signaling through the S1PR3 receptor inhibits MZB migration up the flow, and deletion of S1pr3 in Arhgef6 (−/−) mice rescues mislocalized MZBs. These findings establish shear flow as a directional cue for MZB migration to the follicle, and define S1PR3 and VCAM-1 as counteracting forces that inhibit this migration.
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spelling pubmed-57416192017-12-29 The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling Tedford, Kerry Steiner, Michael Koshutin, Stanislav Richter, Karin Tech, Laura Eggers, Yannik Jansing, Inga Schilling, Kerstin Hauser, Anja Erika Korthals, Mark Fischer, Klaus-Dieter Nat Commun Article Splenic marginal zone B cells (MZB) shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery. However, it is unclear how MZBs migrate directionally from the marginal zone to the follicle. Here, we show that murine MZBs migrate up shear flow via the LFA-1 (αLβ2) integrin ligand ICAM-1, but adhere or migrate down the flow via the VLA-4 integrin (α4β1) ligand VCAM-1. MZBs lacking Arhgef6 (Pak-interacting exchange factor (αPIX)) or functional LFA-1 are impaired in shuttling due to mislocalization toward the VCAM-1-rich red pulp. Sphingosine-1-phosphate (S1P) signaling through the S1PR3 receptor inhibits MZB migration up the flow, and deletion of S1pr3 in Arhgef6 (−/−) mice rescues mislocalized MZBs. These findings establish shear flow as a directional cue for MZB migration to the follicle, and define S1PR3 and VCAM-1 as counteracting forces that inhibit this migration. Nature Publishing Group UK 2017-12-22 /pmc/articles/PMC5741619/ /pubmed/29273735 http://dx.doi.org/10.1038/s41467-017-02482-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tedford, Kerry
Steiner, Michael
Koshutin, Stanislav
Richter, Karin
Tech, Laura
Eggers, Yannik
Jansing, Inga
Schilling, Kerstin
Hauser, Anja Erika
Korthals, Mark
Fischer, Klaus-Dieter
The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
title The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
title_full The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
title_fullStr The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
title_full_unstemmed The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
title_short The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
title_sort opposing forces of shear flow and sphingosine-1-phosphate control marginal zone b cell shuttling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741619/
https://www.ncbi.nlm.nih.gov/pubmed/29273735
http://dx.doi.org/10.1038/s41467-017-02482-4
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