TY - JOUR
T1 - ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs
AU - Mrass, Paulus
AU - Oruganti, Sreenivasa Rao
AU - Fricke, G. Matthew
AU - Tafoya, Justyna
AU - Byrum, Janie R.
AU - Yang, Lihua
AU - Hamilton, Samantha L.
AU - Miller, Mark J.
AU - Moses, Melanie E.
AU - Cannon, Judy L.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031937096&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01032-2
DO - 10.1038/s41467-017-01032-2
M3 - Article
C2 - 29044117
AN - SCOPUS:85031937096
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1010
ER -