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, Judy L. Cannon

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish
Article number1010
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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    Mrass, P., Oruganti, S. R., Fricke, G. M., Tafoya, J., Byrum, J. R., Yang, L., Hamilton, S. L., Miller, M. J., Moses, M. E., & Cannon, J. L. (2017). ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs. Nature communications, 8(1), [1010]. https://doi.org/10.1038/s41467-017-01032-2