CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways
Resident memory T cells (T cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung T cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we s...
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| Vydané v: | The Journal of experimental medicine Ročník 216; číslo 12; s. 2748 |
|---|---|
| Hlavní autori: | , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
02.12.2019
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| ISSN: | 1540-9538, 1540-9538 |
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| Abstract | Resident memory T cells (T
cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung T
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 T
cells have distinct effector functions and that CXCR6 controls the partitioning of T
cells within the lung by recruiting CD8 T
cells to the airways. The absence of CXCR6 significantly decreases airway CD8 T
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 T
cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway T
cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of T
cells to different compartments of the lung and maintains airway T
cells. |
|---|---|
| AbstractList | 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.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. Resident memory T cells (T cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung T 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 T cells have distinct effector functions and that CXCR6 controls the partitioning of T cells within the lung by recruiting CD8 T cells to the airways. The absence of CXCR6 significantly decreases airway CD8 T 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 T cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway T cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of T cells to different compartments of the lung and maintains airway T cells. |
| Author | Masumoto, Tomoko McManus, Daniel T Dunbar, Paul R Hayward, Sarah L Takamura, Shiki Wein, Alexander N McMaster, Sean R Tsukui, Tatsuya Matsushima, Kouji Ueha, Satoshi Cartwright, Emily K Shimaoka, Takeshi Kohlmeier, Jacob E Kurachi, Makoto |
| Author_xml | – sequence: 1 givenname: Alexander N orcidid: 0000-0002-8813-3523 surname: Wein fullname: Wein, Alexander N organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA – sequence: 2 givenname: Sean R surname: McMaster fullname: McMaster, Sean R organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA – sequence: 3 givenname: Shiki orcidid: 0000-0001-6681-0258 surname: Takamura fullname: Takamura, Shiki organization: Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan – sequence: 4 givenname: Paul R orcidid: 0000-0002-9082-6636 surname: Dunbar fullname: Dunbar, Paul R organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA – sequence: 5 givenname: Emily K surname: Cartwright fullname: Cartwright, Emily K organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA – sequence: 6 givenname: Sarah L orcidid: 0000-0001-7052-5556 surname: Hayward fullname: Hayward, Sarah L organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA – sequence: 7 givenname: Daniel T surname: McManus fullname: McManus, Daniel T organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA – sequence: 8 givenname: Takeshi surname: Shimaoka fullname: Shimaoka, Takeshi organization: Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan – sequence: 9 givenname: Satoshi surname: Ueha fullname: Ueha, Satoshi organization: Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan – sequence: 10 givenname: Tatsuya surname: Tsukui fullname: Tsukui, Tatsuya organization: Department of Medicine, University of California, San Francisco, San Francisco, CA – sequence: 11 givenname: Tomoko surname: Masumoto fullname: Masumoto, Tomoko organization: Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan – sequence: 12 givenname: Makoto surname: Kurachi fullname: Kurachi, Makoto organization: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA – sequence: 13 givenname: Kouji surname: Matsushima fullname: Matsushima, Kouji organization: Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan – sequence: 14 givenname: Jacob E orcidid: 0000-0002-7209-6641 surname: Kohlmeier fullname: Kohlmeier, Jacob E email: jkohlmeier@emory.edu organization: Emory-UGA Center of Excellence for Influenza Research and Surveillance, Atlanta, GA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31558615$$D View this record in MEDLINE/PubMed |
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| Snippet | Resident memory T cells (T
cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung T
cell populations to... Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell... |
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| Title | CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways |
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