Abstract

Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood. Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue. Computational analysis indicates that T cells migrate with an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature. Rho-associated protein kinase (ROCK) is required for both high-speed migration and straight motion. By contrast, inhibition of Gαi signaling with pertussis toxin affects speed but not the intermittent migration of lung-infiltrating T cells. Computational modeling shows that an intermittent migration pattern balances both search area and the duration of contacts between T cells and target cells. These data identify that ROCK-dependent intermittent T cell migration regulates tissue-sampling during acute lung injury.

Details

Title
ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs
Author
Paulus Mrass 1   VIAFID ORCID Logo  ; Sreenivasa Rao Oruganti 1 ; Fricke, G Matthew 2 ; Tafoya, Justyna 3 ; Byrum, Janie R 1   VIAFID ORCID Logo  ; Yang, Lihua 4 ; Hamilton, Samantha L 4 ; Miller, Mark J 4 ; Moses, Melanie E 5 ; Cannon, Judy L 1   VIAFID ORCID Logo 

1  Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, USA 
2  Department of Computer Science, University of New Mexico, Albuquerque, NM, USA 
3  Department of Computer Science, University of New Mexico, Albuquerque, NM, USA; Department of Mathematics, University of New Mexico, Albuquerque, NM, USA 
4  Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA 
5  Department of Computer Science, University of New Mexico, Albuquerque, NM, USA; Department of Biology, University of New Mexico, Albuquerque, NM, USA; External Faculty, Santa Fe Institute, Santa Fe, NM, USA 
Pages
1-14
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-01032-2
ProQuest document ID
1952473463
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.