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Dendritic cells control fibroblastic reticular network tension and lymph node expansion

Acton, SE; Farrugia, AJ; Astarita, JL; Mourão-Sá, D; Jenkins, RP; Nye, E; Hooper, S; ... Reis e Sousa, C; + view all (2014) Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature , 514 (7523) pp. 498-502. 10.1038/nature13814. Green open access

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Abstract

After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion1, 2. Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes3 also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion—driven by lymphocyte influx and proliferation—that is the critical hallmark of adaptive immunity.

Type: Article
Title: Dendritic cells control fibroblastic reticular network tension and lymph node expansion
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nature13814
Publisher version: http://dx.doi.org/10.1038/nature13814
Language: English
Additional information: Copyright © 2014 Macmillan Publishers Limited. All rights reserved.
Keywords: Lymph node, Acute inflammation, Actin, Cellular imaging
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/1474043
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