IL-17-producing gamma delta Tcells switch migratory patterns between resting and activated states

McKenzie, Duncan R. and Kara, Ervin E. and Bastow, Cameron R. and Tyllis, Timona S. and Fenix, Kevin A. and Gregor, Carly E. and Wilson, Jasmine J. and Babb, Rachelle and Paton, James C. and Kallies, Axel and Nutt, Stephen L. and Brustle, Anne and Mack, Matthias and Comerford, Iain and McColl, Shaun R. (2017) IL-17-producing gamma delta Tcells switch migratory patterns between resting and activated states. NATURE COMMUNICATIONS, 8: 15632. ISSN 2041-1723,

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Abstract

Interleukin 17-producing gamma delta T (gamma delta T17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to gamma delta T17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling gamma delta T17 cell positioning in barrier tissues and recruitment to inflammatory sites are still unclear. Here we show that gamma delta T17 cells constitutively express chemokine receptors CCR6 and CCR2. While CCR6 recruits resting gamma delta T17 cells to the dermis, CCR2 drives rapid gamma delta T17 cell recruitment to inflamed tissues during autoimmunity, cancer and infection. Downregulation of CCR6 by IRF4 and BATF upon gamma delta T17 activation is required for optimal recruitment of gamma delta T17 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 gamma delta T17 cells to inflammatory lesions.

Item Type: Article
Uncontrolled Keywords: EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PSORIASIFORM SKIN INFLAMMATION; T-CELL SUBSETS; DENDRITIC CELLS; INTERFERON-GAMMA; LYMPH-NODES; TH17 CELLS; DIFFERENTIATION; PROMOTE; ARTHRITIS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:10
Last Modified: 25 Feb 2019 11:49
URI: https://pred.uni-regensburg.de/id/eprint/716

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