CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways

• Type of Material: Article
• Authors: Alexander N. Wein, Emory University; Sean R. McMaster, Emory University; Shiki Takamura, Kindai University; Paul R. Dunbar, Emory University; Emily K. Cartwright, Emory University; Sarah L. Hayward, Emory University; Daniel T. McManus, Emory University; Takeshi Shimaoka, Tokyo University of Science; Satoshi Ueha, Tokyo University of Science; Tatsuya Tsukui, University of California San Francisco; Tomoko Masumoto, Kindai University; Makoto Kurachi, University of Pennsylvania; Kouji Matsushima, Tokyo University of Science; Jacob Kohlmeier, Emory University
• Language: English
• Date: 2019-12-01
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Wein et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20181308
• Title of Journal or Parent Work: Journal of Experimental Medicine
• Volume: 216
• Issue: 12
• Start Page: 2748
• End Page: 2762
• Grant/Funding Information: This project was supported by National Institutes of Health grants HL122559 and HL138508 and Centers of Excellence in Influenza Research and Surveillance contract HHSN272201400004C (to J.E. Kohlmeier);; P.R. Dunbar was supported by National Institutes of Health grant F31 AI124611, and S.L. Hayward was supported by F31 HL136101.; S.R. McMaster was supported by National Institutes of Health grants F30 HL118954 and T32 AI007610.; Ministry of Education, Culture, Sports, Science and Technology of Japan Grant-in-Aid for Young Scientists (A) 24689043 and Grant-in-Aid for Scientific Research (C) 16K08850;; We recognize contributions from the Children's Healthcare of Atlanta and Emory University Pediatric Flow Cytometry Core for cell sorting and the National Institutes of Health Tetramer Core Facility (contract HHSN272201300006C).; Grants from Takeda Science Foundation, Daiichi-Sankyo Foundation of Life Science, Uehara Memorial Foundation, and Kanae Foundation for Promotion of Medical Science.
• Keywords: Medicine, Research & Experimental; Ligand CXCL16; Immunology; Chemokine receptor CXCR6; Cutting edge; Expression; Antigen; IFN-gamma; Research & Experimental Medicine; Science & Technology; Lung; Activation; Life Sciences & Biomedicine; Maintenance; Protection
• Research Categories: Biology, Genetics; Biology, Cell; Biology, Microbiology; Health Sciences, Immunology

Abstract

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.