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Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9

De Winde, CM; Makris, S; Millward, LJ; Cantoral-Rebordinos, JA; Benjamin, AC; Martínez, VG; Acton, SE; (2021) Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9. Journal of Cell Science , 134 (14) , Article jcs258610. 10.1242/jcs.258610. Green open access

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Abstract

In adaptive immunity, CLEC-2+ dendritic cells (DCs) contact fibroblastic reticular cells (FRCs) inhibiting podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. The molecular mechanisms controlling lymph node remodelling are incompletely understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion, and which other proteins are required for the FRC response to DCs. We find that podoplanin and its partner proteins CD44 and CD9 are differentially expressed by specific lymph node stromal populations in vivo, and their expression in FRCs is coregulated by CLEC-2 (encoded by CLEC1B). Both CD44 and CD9 suppress podoplanin-dependent contractility. We find that beyond contractility, podoplanin is required for FRC polarity and alignment. Independently of podoplanin, CD44 and CD9 affect FRC–FRC interactions. Furthermore, our data show that remodelling of the FRC cytoskeleton in response to DCs is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2 and podoplanin binding inhibits FRC contractility, and, secondly, FRCs form protrusions and spread, which requires both CD44 and CD9. Together, we show a multi-faceted FRC response to DCs, which requires CD44 and CD9 in addition to podoplanin.

Type: Article
Title: Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.258610
Publisher version: https://doi.org/10.1242/jcs.258610
Language: English
Additional information: Copyright © 2021. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Fibroblastic reticular cell, Lymph node, Podoplanin, CD44, CD9, Tetraspanins, Dendritic cell
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10133047
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