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Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules

Nature volume 479, pages 542–546 (2011)Cite this article

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Abstract

While patrolling the body in search of foreign antigens, naive lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood1,2. This process, called lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body’s own cells. However, the mechanisms that regulate lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T lymphocytes3, control the entry of naive lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in lymphocyte recruitment2,4,5. We found that in vivo depletion of CD11c+ DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-β-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of lymphocyte recirculation during immune surveillance.

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Figure 1: CD11c + DCs are required for lymphocyte homing to lymph nodes.
Figure 2: CD11c + DCs are essential for the homeostatic maintenance of HEV phenotype.
Figure 3: CD11c + DCs control the rolling velocity and firm adhesion of lymphocytes inside PLN HEVs.
Figure 4: DC-derived LT is important for lymphocyte homing to lymph nodes in vivo.

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Acknowledgements

We are grateful to S. Rosen, J. Lowe and J. Browning for the gift of antibodies, to H. Korner, T. Winkler, E. Donnadieu, M. Lipp, O. Lantz, B. Ryffel, L. Brault, S. A. Nedospasov and S. Jung for providing mice, to J. van Meerwijk for critical reading of the manuscript, and to N. Ortega, E. Bellard and F. El-Fahqui-Olive for help with immunohistochemistry, intravital microscopy and cell sorting, respectively. We thank the IPBS TRI imaging facility, A. Dujardin and the IPBS animal and transgenic facilities for help with animal experiments, and F. Viala for preparation of the figures. This work was supported by grants from the Ligue Nationale Contre le Cancer (Equipe labellisée Ligue 2009 to J.-P.G.) and the Association pour la Recherche contre le Cancer (ARC, equipment 8505). C.M. was supported by fellowships from the French Ministry of Research, the ARC and Fondation RITC.

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Authors and Affiliations

  1. CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne, F-31077 Toulouse, France

    Christine Moussion & Jean-Philippe Girard

  2. Université de Toulouse, UPS, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France

    Christine Moussion & Jean-Philippe Girard

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  1. Christine Moussion
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  2. Jean-Philippe Girard
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C.M. designed the study, performed all of the experiments and analysed the data. J.-P.G. designed the study, analysed the data and wrote the paper.

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Correspondence to Jean-Philippe Girard.

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Moussion, C., Girard, JP. Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules. Nature 479, 542–546 (2011). https://doi.org/10.1038/nature10540

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