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.
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.
Cell Rep. 2024 Aug 27;43(8):114620. doi: 10.1016/j.celrep.2024.114620. Epub 2024 Aug 13.
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.
嗜酸性粒细胞参与宿主对多细胞生物的保护。然而，它们在 2 型免疫中向肠系膜淋巴结 (mLN) 的募集尚未得到充分研究。我们的结果表明，在选择性缺乏 B 细胞上表达白细胞介素 (IL)-4Rα 或淋巴毒素-β (LTβ) 的小鼠中，嗜酸性粒细胞与成纤维网状细胞 (FRC) 和淋巴内皮细胞构建的淋巴样基质龛的关联减少。此外，嗜酸性粒细胞的存活、激活和 Il1rl1 受体表达的增强是由基质细胞和 B 细胞对话驱动的。FRC 上的淋巴毒素-β 受体 (LTβR) 的交联可改善嗜酸性粒细胞的存活，并显著增强 IL-33 的表达和嗜酸性粒细胞向 mLN 的归巢，从而证实淋巴毒素信号对粒细胞募集的重要性。缺乏嗜酸性粒细胞的 ΔdblGATA-1 小鼠表现出 mLN 扩张减少、滤泡间区域 (IFR) 警报素表达减少和寄生虫清除延迟，阐明了它们在 2 型免疫中的重要性。这些发现为基质细胞和 B 细胞之间的对话提供了深入了解，这些对话控制着 mLN 嗜酸性粒细胞增多症，以及这些机制在 2 型免疫中的相关性。
