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

Author

Listed:
  • Paulus Mrass

    (University of New Mexico School of Medicine)

  • Sreenivasa Rao Oruganti

    (University of New Mexico School of Medicine)

  • G. Matthew Fricke

    (University of New Mexico)

  • Justyna Tafoya

    (University of New Mexico
    University of New Mexico)

  • Janie R. Byrum

    (University of New Mexico School of Medicine)

  • Lihua Yang

    (Division of Infectious Diseases, Washington University School of Medicine)

  • Samantha L. Hamilton

    (Division of Infectious Diseases, Washington University School of Medicine)

  • Mark J. Miller

    (Division of Infectious Diseases, Washington University School of Medicine)

  • Melanie E. Moses

    (University of New Mexico
    University of New Mexico
    External Faculty, Santa Fe Institute)

  • Judy L. Cannon

    (University of New Mexico School of Medicine)

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.

Suggested Citation

  • 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, 2017. "ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01032-2
    DOI: 10.1038/s41467-017-01032-2
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