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IL-17-producing γδ T cells switch migratory patterns between resting and activated states

Author

Listed:
  • Duncan R. McKenzie

    (University of Adelaide)

  • Ervin E. Kara

    (University of Adelaide
    Present address: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.)

  • Cameron R. Bastow

    (University of Adelaide)

  • Timona S. Tyllis

    (University of Adelaide)

  • Kevin A. Fenix

    (University of Adelaide)

  • Carly E. Gregor

    (University of Adelaide)

  • Jasmine J. Wilson

    (University of Adelaide)

  • Rachelle Babb

    (University of Adelaide
    Present address: Department of Medicine, Albert Einstein College of Medicine, New York, New York 10561, USA.)

  • James C. Paton

    (University of Adelaide
    Research Centre for Infectious Diseases, University of Adelaide)

  • Axel Kallies

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Stephen L. Nutt

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Anne Brüstle

    (John Curtin School of Medical Research, Australian National University)

  • Matthias Mack

    (University Hospital Regensburg)

  • Iain Comerford

    (University of Adelaide)

  • Shaun R. McColl

    (University of Adelaide
    Centre for Molecular Pathology, University of Adelaide)

Abstract

Interleukin 17-producing γδ T (γδT17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to γδT17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling γδT17 cell positioning in barrier tissues and recruitment to inflammatory sites are still unclear. Here we show that γδT17 cells constitutively express chemokine receptors CCR6 and CCR2. While CCR6 recruits resting γδT17 cells to the dermis, CCR2 drives rapid γδT17 cell recruitment to inflamed tissues during autoimmunity, cancer and infection. Downregulation of CCR6 by IRF4 and BATF upon γδT17 activation is required for optimal recruitment of γδT17 cells to inflamed tissue by preventing their sequestration into uninflamed dermis. These findings establish a lymphocyte trafficking model whereby a hierarchy of homing signals is prioritized by dynamic receptor expression to drive both tissue surveillance and rapid recruitment of γδT17 cells to inflammatory lesions.

Suggested Citation

  • Duncan R. McKenzie & Ervin E. Kara & Cameron R. Bastow & Timona S. Tyllis & Kevin A. Fenix & Carly E. Gregor & Jasmine J. Wilson & Rachelle Babb & James C. Paton & Axel Kallies & Stephen L. Nutt & Ann, 2017. "IL-17-producing γδ T cells switch migratory patterns between resting and activated states," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15632
    DOI: 10.1038/ncomms15632
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