Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance

Rieke Martens, Marc Permanyer, Kathrin Werth, Kai Yu, Asolina Braun, Olga Halle, Stephan Halle, Gwendolyn E. Patzer, Berislav Bošnjak, Friedemann Kiefer, Anika Janssen, Michaela Friedrichsen, Jenny Poetzsch, Karan Kohli, Yvonne Lueder, Rodrigo Gutierrez Jauregui, Nadine Eckert, Tim Worbs, Melanie Galla and Reinhold Förster ()
Additional contact information
Rieke Martens: Hannover Medical School
Marc Permanyer: Hannover Medical School
Kathrin Werth: Hannover Medical School
Kai Yu: Hannover Medical School
Asolina Braun: Hannover Medical School
Olga Halle: Hannover Medical School
Stephan Halle: Hannover Medical School
Gwendolyn E. Patzer: Hannover Medical School
Berislav Bošnjak: Hannover Medical School
Friedemann Kiefer: Max Planck Institute for Molecular Biomedicine
Anika Janssen: Hannover Medical School
Michaela Friedrichsen: Hannover Medical School
Jenny Poetzsch: Hannover Medical School
Karan Kohli: Hannover Medical School
Yvonne Lueder: Hannover Medical School
Rodrigo Gutierrez Jauregui: Hannover Medical School
Nadine Eckert: Hannover Medical School
Tim Worbs: Hannover Medical School
Melanie Galla: Hannover Medical School
Reinhold Förster: Hannover Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Little is known regarding lymph node (LN)-homing of immune cells via afferent lymphatics. Here, we show, using a photo-convertible Dendra-2 reporter, that recently activated CD4 T cells enter downstream LNs via afferent lymphatics at high frequencies. Intra-lymphatic immune cell transfer and live imaging data further show that activated T cells come to an instantaneous arrest mediated passively by the mechanical 3D-sieve barrier of the LN subcapsular sinus (SCS). Arrested T cells subsequently migrate randomly on the sinus floor independent of both chemokines and integrins. However, chemokine receptors are imperative for guiding cells out of the SCS, and for their subsequent directional translocation towards the T cell zone. By contrast, integrins are dispensable for LN homing, yet still contribute by increasing the dwell time within the SCS and by potentially enhancing T cell sensing of chemokine gradients. Together, these findings provide fundamental insights into mechanisms that control homing of lymph-derived immune cells.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14921-w

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DOI: 10.1038/s41467-020-14921-w

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