Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Elizabeth E Gray
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Hsin Chen
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Lauren B Rodda
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Yin Liang
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Patrick Ventura
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
Saul Villeda
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
Paul R Crocker
Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom; College of Life Sciences, University of Dundee, Dundee, United Kingdom
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.
