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

Nat Commun. 2017 Oct 18;8(1):1010. doi: 10.1038/s41467-017-01032-2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Algorithms
  • Animals
  • Cell Movement*
  • Cell Tracking / methods
  • Female
  • Lung / diagnostic imaging
  • Lung / metabolism
  • Lung / pathology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • T-Lymphocytes / metabolism*
  • rho-Associated Kinases / metabolism*

Substances

  • rho-Associated Kinases