Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we show that airway and interstitial TRM cells have distinct effector functions and that CXCR6 controls the partitioning of TRM cells within the lung by recruiting CD8 TRM cells to the airways. The absence of CXCR6 significantly decreases airway CD8 TRM cells due to altered trafficking of CXCR6−/− cells within the lung, and not decreased survival in the airways. CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 TRM cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway TRM cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of TRM cells to different compartments of the lung and maintains airway TRM cells.
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September 26 2019
CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways
Alexander N. Wein
,
Alexander N. Wein
*
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
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Sean R. McMaster
,
Sean R. McMaster
*
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
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Shiki Takamura
,
Shiki Takamura
*
2
Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
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Paul R. Dunbar
,
Paul R. Dunbar
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
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Emily K. Cartwright
,
Emily K. Cartwright
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
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Sarah L. Hayward
,
Sarah L. Hayward
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
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Daniel T. McManus
,
Daniel T. McManus
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
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Takeshi Shimaoka
,
Takeshi Shimaoka
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
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Satoshi Ueha
,
Satoshi Ueha
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
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Tatsuya Tsukui
,
Tatsuya Tsukui
4
Department of Medicine, University of California, San Francisco, San Francisco, CA
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Tomoko Masumoto
,
Tomoko Masumoto
2
Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
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Makoto Kurachi
,
Makoto Kurachi
5
Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Kouji Matsushima
,
Kouji Matsushima
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
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Jacob E. Kohlmeier
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
6
Emory-UGA Center of Excellence for Influenza Research and Surveillance, Atlanta, GA
Correspondence to Jacob E. Kohlmeier: jkohlmeier@emory.edu
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Alexander N. Wein
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
Sean R. McMaster
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
Shiki Takamura
2
Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
Paul R. Dunbar
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
Emily K. Cartwright
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
Sarah L. Hayward
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
Daniel T. McManus
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
Takeshi Shimaoka
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
Satoshi Ueha
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
Tatsuya Tsukui
4
Department of Medicine, University of California, San Francisco, San Francisco, CA
Tomoko Masumoto
2
Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
Makoto Kurachi
5
Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Kouji Matsushima
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
Jacob E. Kohlmeier
1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA
6
Emory-UGA Center of Excellence for Influenza Research and Surveillance, Atlanta, GA
*
A.N. Wein, S.R. McMaster, and S. Takamura contributed equally to this paper.
Correspondence to Jacob E. Kohlmeier: jkohlmeier@emory.edu
J Exp Med (2019) 216 (12): 2748-2762.
Article history
Received:
July 10 2018
Revision Received:
January 14 2019
Accepted:
August 13 2019
Citation
Alexander N. Wein, Sean R. McMaster, Shiki Takamura, Paul R. Dunbar, Emily K. Cartwright, Sarah L. Hayward, Daniel T. McManus, Takeshi Shimaoka, Satoshi Ueha, Tatsuya Tsukui, Tomoko Masumoto, Makoto Kurachi, Kouji Matsushima, Jacob E. Kohlmeier; CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways. J Exp Med 2 December 2019; 216 (12): 2748–2762. doi: https://doi.org/10.1084/jem.20181308
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