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Nature Research, Nature, 7523(514), p. 498-502, 2014

DOI: 10.1038/nature13814

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Dendritic Cells Control Fibroblastic Reticular Network Tension and Lymph Node Expansion

Journal article published in 2014 by Sophie E. Acton, Aaron J. Farrugia, Jillian L. Astarita, Diego Mourão-Sá, Robert P. Jenkins, Emma Nye, Steven Hooper, Janneke van Blijswijk, Neil C. Rogers, Kathryn J. Snelgrove, Ian Rosewell, Luis F. Moita ORCID, Gordon Stamp, Shannon J. Turley, Erik Sahai and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion(1,2). 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 lymphocytes(3) 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.