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- Title
ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs.
- Authors
Mrass, Paulus; Oruganti, Sreenivasa Rao; Fricke, G. Matthew; Tafoya, Justyna; Byrum, Janie R.; Lihua Yang; Hamilton, Samantha L.; Miller, Mark J.; Moses, Melanie E.; Cannon, Judy L.
- 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 Gai 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.
- Subjects
INTERSTITIAL cells; CELL migration; RHO-associated kinases; PERTUSSIS toxin; PROTEIN kinases; EXTRACELLULAR fluid; T cells; ANIMAL migration
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01032-2