title: Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node.
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 IL7R(hi)Ccr6(+) 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.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Yang
authors.identifier: 0000-0003-4355-9755
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Theodore L
authors.identifier: 0000-0002-3970-9573
authors.initials: TL
authors.lastname: Roth
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Gray
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Hsin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Rodda
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Yin
authors.initials: Y
authors.lastname: Liang
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ventura
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States.
authors.forename: Saul
authors.initials: S
authors.lastname: Villeda
authors.affiliation: Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom.|College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Jason G
authors.identifier: 0000-0003-2345-629X
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D002448:Cell Adhesion; D002465:Cell Movement; D005658:Fungi / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D054399:Receptors, CCR6 / Q000032:analysis; D020395:Receptors, Interleukin-7 / Q000032:analysis
chemical_list: C498126:CCR6 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D054399:Receptors, CCR6; D020395:Receptors, Interleukin-7
keywords: CD169; IL17; SCS Macrophage; immunology; innate like lymphocytes; lymph node; migration; mouse