Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node
- Howard Hughes Medical Institute, University of California, San Francisco, United States
- University of Washington School of Medicine, United States
- University of California, San Francisco, United States
- University of Dundee, United Kingdom
Abstract
Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular sinus (SCS) and associated macrophages for pathogen entry. The factors promoting this surveillance behavior have not been defined. Here we report that IL7RhiCcr6+ lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal challenge. We show that these innate-like lymphocytes are mostly LN resident. Ccr6 is required for their accumulation near the SCS and for efficient IL17 induction. Migration into the SCS intrinsically requires S1pr1 whereas movement from the sinus into the parenchyma involves the integrin LFA1 and its ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within the sinus, preventing their loss in lymph flow. These findings establish a role for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens, and they define requirements for cell movement between parenchyma and SCS in what we speculate is a program of immune surveillance that helps achieve LN barrier immunity.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Yang Zhang
- Theodore L Roth
- Elizabeth E Gray
- Hsin Chen
- Lauren B Rodda
- Jason G Cyster
National Institutes of Health (AI074847)
- Jason G Cyster
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals were housed in a specific pathogen-free environment in the Laboratory Animal Research Center at the University of California San Francisco (UCSF), and all experiments conformed to the ethical principles and guidelines approved by the UCSF Institutional and Animal Care and Use Committee, protocol approval number: AN107975-02.
Copyright
© 2016, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node
eLife 5:e18156.
https://doi.org/10.7554/eLife.18156
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The factors that regulate how immune cells called innate-like lymphocytes are localized in the tissue have been identified.
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