Stromal cell and B cell dialogue potentiates IL-33-enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity
Emily Bessell,
Rachel E. Finlay,
Louisa K. James,
Burkhard Ludewig,
Nicola L. Harris,
Philippe Krebs,
Matthew R. Hepworth,
Lalit Kumar Dubey
Affiliations
Emily Bessell
William Harvey Research Institute (WHRI), Barts & The London School of Medicine & Dentistry, Queen Mary University of London (QMUL), London, UK; Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland; Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
Rachel E. Finlay
Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, UK
Louisa K. James
Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK
Burkhard Ludewig
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
Nicola L. Harris
Department of Immunology and Pathology, Central Clinical School, Monash University, The Alfred Centre, Melbourne, VIC, Australia
Philippe Krebs
Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
Matthew R. Hepworth
Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, UK
Lalit Kumar Dubey
William Harvey Research Institute (WHRI), Barts & The London School of Medicine & Dentistry, Queen Mary University of London (QMUL), London, UK; Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland; Corresponding author
Summary: Eosinophils are involved in host protection against multicellular organisms. However, their recruitment to the mesenteric lymph node (mLN) during type 2 immunity is understudied. Our results demonstrate that eosinophil association with lymphoid stromal niches constructed by fibroblastic reticular cells (FRCs) and lymphatic endothelial cells is diminished in mice selectively lacking interleukin (IL)-4Rα or lymphotoxin-β (LTβ) expression on B cells. Furthermore, eosinophil survival, activation, and enhanced Il1rl1 receptor expression are driven by stromal cell and B cell dialogue. The ligation of lymphotoxin-β receptor (LTβR) on FRCs improves eosinophil survival and significantly augments IL-33 expression and eosinophil homing to the mLN, thus confirming the significance of lymphotoxin signaling for granulocyte recruitment. Eosinophil-deficient ΔdblGATA-1 mice show diminished mLN expansion, reduced interfollicular region (IFR) alarmin expression, and delayed helminth clearance, elucidating their importance in type 2 immunity. These findings provide insight into dialogue between stromal cells and B cells, which govern mLN eosinophilia, and the relevance of these mechanisms during type 2 immunity.
