Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 02 2020
28 02 2020
Historique:
received:
03
05
2019
accepted:
09
02
2020
entrez:
1
3
2020
pubmed:
1
3
2020
medline:
27
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32111837
doi: 10.1038/s41467-020-14921-w
pii: 10.1038/s41467-020-14921-w
pmc: PMC7048855
doi:
Substances chimiques
Chemokines
0
Integrins
0
Receptors, Chemokine
0
Receptors, Lymphocyte Homing
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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