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J Exp Med. 2018 Nov 5;215(11):2760-2777. doi: 10.1084/jem.20180217. Epub 2018 Oct 24.

Multiple roles of lymphatic vessels in peripheral lymph node development.

Author information

1
Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland.
2
School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea.
3
Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
4
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
5
Max Planck Institute for Molecular Biomedicine, Münster, Germany.
6
European Institute for Molecular Imaging, University of Münster, Münster, Germany.
7
Integrated Cardio Metabolic Centre, Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
8
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
9
Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland tatiana.petrova@unil.ch.
10
Ludwig Institute for Cancer Research, Epalinges, Switzerland.
11
Swiss Institute for Experimental Cancer Research, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
12
Division of Experimental Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Abstract

The mammalian lymphatic system consists of strategically located lymph nodes (LNs) embedded into a lymphatic vascular network. Mechanisms underlying development of this highly organized system are not fully understood. Using high-resolution imaging, we show that lymphoid tissue inducer (LTi) cells initially transmigrate from veins at LN development sites using gaps in venous mural coverage. This process is independent of lymphatic vasculature, but lymphatic vessels are indispensable for the transport of LTi cells that egress from blood capillaries elsewhere and serve as an essential LN expansion reservoir. At later stages, lymphatic collecting vessels ensure efficient LTi cell transport and formation of the LN capsule and subcapsular sinus. Perinodal lymphatics also promote local interstitial flow, which cooperates with lymphotoxin-β signaling to amplify stromal CXCL13 production and thereby promote LTi cell retention. Our data unify previous models of LN development by showing that lymphatics intervene at multiple points to assist LN expansion and identify a new role for mechanical forces in LN development.

PMID:
30355615
PMCID:
PMC6219737
[Available on 2019-05-05]
DOI:
10.1084/jem.20180217

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