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

Mrass, Paulus; Oruganti, Sreenivasa Rao; Fricke, G. Matthew; Tafoya, Justyna; Byrum, Janie R.; Yang, Lihua; Hamilton, Samantha L.; Miller, Mark J.; Moses, Melanie E.; Cannon, Judy L.

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 Gα(i) 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.