Stromal cell and B cell dialogue potentiates IL-33-enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity

Cell Rep. 2024 Aug 27;43(8):114620. doi: 10.1016/j.celrep.2024.114620. Epub 2024 Aug 13.

Abstract

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.

Keywords: B cell; CCL24; CP: Immunology; Heligmosomoides polygyrus; IL-33; IL-4Rα; eosinophils; fibroblastic reticular cells; lymphatic endothelial cells; mesenteric lymph node; stromal cells.

MeSH terms

  • Animals
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / metabolism
  • Cell Communication
  • Eosinophils* / immunology
  • Eosinophils* / metabolism
  • Interleukin-1 Receptor-Like 1 Protein / genetics
  • Interleukin-1 Receptor-Like 1 Protein / metabolism
  • Interleukin-33* / metabolism
  • Lymph Nodes / immunology
  • Lymphotoxin beta Receptor / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Cell Surface
  • Signal Transduction
  • Stromal Cells* / immunology
  • Stromal Cells* / metabolism

Substances

  • Interleukin-33
  • Lymphotoxin beta Receptor
  • Interleukin-1 Receptor-Like 1 Protein
  • Il1rl1 protein, mouse
  • Il4ra protein, mouse
  • Il33 protein, mouse
  • Receptors, Cell Surface