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

First Author  Martens R Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  1114
PubMed ID  32111837 Mgi Jnum  J:286734
Mgi Id  MGI:6401765 Doi  10.1038/s41467-020-14921-w
Citation  Martens R, et al. (2020) Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance. Nat Commun 11(1):1114
abstractText  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.
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