IL-17-producing γδ T cells switch migratory patterns between resting and activated states
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Date
2017
Authors
McKenzie, D.
Kara, E.
Bastow, C.
Tyllis, T.
Fenix, K.
Gregor, C.
Wilson, J.
Babb, R.
Paton, J.
Kallies, A.
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Journal article
Citation
Nature Communications, 2017; 8(15632):15632-1-15632-13
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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, Anne Brüstle, Matthias Mack, Iain Comerford, Shaun R. McColl
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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.
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Data source: Supplementary information, https://doi.org/10.1038/ncomms15632
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© The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/