ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs

Paulus Mrass, Sreenivasa Rao Oruganti, G. Matthew Fricke, Justyna Tafoya, Janie R. Byrum, Lihua Yang, Samantha L. Hamilton, Mark J. Miller, Melanie E. Moses and Judy L. Cannon ()
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Paulus Mrass: University of New Mexico School of Medicine
Sreenivasa Rao Oruganti: University of New Mexico School of Medicine
G. Matthew Fricke: University of New Mexico
Justyna Tafoya: University of New Mexico
Janie R. Byrum: University of New Mexico School of Medicine
Lihua Yang: Division of Infectious Diseases, Washington University School of Medicine
Samantha L. Hamilton: Division of Infectious Diseases, Washington University School of Medicine
Mark J. Miller: Division of Infectious Diseases, Washington University School of Medicine
Melanie E. Moses: University of New Mexico
Judy L. Cannon: University of New Mexico School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01032-2

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