De Winde, Charlotte;
Makris, Spyridon;
Millward, Lindsey;
Rebordinos, Jesús Cantoral;
Benjamin, Agnesska;
Martínez, Víctor;
Acton, Sophie;
(2020)
Fibroblastic Reticular Cell Response to Dendritic Cells Requires Coordinated Activity of Podoplanin, CD44 and CD9.
BioRxiv: Cold Spring Harbor, NY, USA.
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Abstract
Lymph node expansion is pivotal for adaptive immunity. CLEC-2+ migratory dendritic cells (DCs) interact with fibroblastic reticular cells (FRCs) to inhibit podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. However, the molecular mechanisms controlling lymph node remodelling are not fully understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion in vivo, and further, which other FRC markers are required for FRCs to respond to CLEC-2+ DCs. We find that expression of podoplanin and its partner proteins CD44 and CD9 in FRCs is coregulated by CLEC-2, and is differentially expressed by specific lymph node stromal populations in vivo. We find that beyond contractility, podoplanin is required for polarity and alignment of FRCs. Both CD44 and CD9 act to dampen podoplanin-dependent contractility, and colocalize with podoplanin in different areas of the cell membrane. Independently of podoplanin, CD44 and CD9 affect the degree of cell-cell contact and overlap between neighbouring FRCs. Further, we show that both CD44 and CD9 are required for FRCs to spread and form protrusions in response to DCs. Our data show that remodelling of the FRC cytoskeleton is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2/podoplanin-binding drives relaxation of actomyosin contractility, and secondly FRCs form protrusions and spread which requires both CD44 and CD9. Together, we show a multi-faceted response of FRCs to DCs, which requires CD44 and CD9 in addition to podoplanin.
| Type: | Working / discussion paper |
|---|---|
| Title: | Fibroblastic Reticular Cell Response to Dendritic Cells Requires Coordinated Activity of Podoplanin, CD44 and CD9 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/793141 |
| Publisher version: | https://doi.org/10.1101/793141 |
| Language: | English |
| Additional information: | The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license (http://creativecommons.org/licenses/by-nd/4.0/). |
| 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 > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10180827 |
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