Li Conglei, Ward Lesley A, Nguyen Albert, Lam Evelyn, Dasoveanu Dragos, Ahmed Musaddeque, Haniuda Kei, Buechler Matthew B, He Housheng Hansen, Ludewig Burkhard, McNagny Kelly Marshall, Gommerman Jennifer L
Department of Immunology, University of Toronto, Toronto, ON, Canada.
School of Medicine, The Chinese University of Hong Kong, Shenzhen, China.
Mucosal Immunol. 2022 Mar;15(3):418-427. doi: 10.1038/s41385-022-00493-z. Epub 2022 Feb 18.
Although eosinophils are important contributors to mucosal immune responses, mechanisms that regulate their accumulation in mucosal-associated lymphoid tissues remain ill-defined. Combining bone marrow chimeras and pharmacological inhibition approaches, here we find that lymphotoxin-beta receptor (LTβR) signaling during the neonatal period is required for the accumulation of eosinophils in the mesenteric lymph nodes (MLN) during an enteric viral infection in adult male and female mice. We demonstrate that MLN stromal cells express genes that are important for eosinophil migration and survival, such as Ccl-11 (eotaxin-1), Ccl7, Ccl9, and Cxcl2, and that expression of most of these genes is downregulated as a consequence of neonatal LTβR blockade. We also find that neonatal LTβR signaling is required for the generation of a rotavirus-specific IgA antibody response in the adult MLN, but eosinophils are dispensable for this response. Collectively, our studies reveal a role for neonatal LTβR signaling in regulating eosinophil numbers in the adult MLN.
尽管嗜酸性粒细胞是黏膜免疫反应的重要参与者，但调节其在黏膜相关淋巴组织中积聚的机制仍不清楚。通过结合骨髓嵌合体和药理学抑制方法，我们发现，在成年雄性和雌性小鼠发生肠道病毒感染期间，新生期的淋巴毒素-β受体（LTβR）信号传导是嗜酸性粒细胞在肠系膜淋巴结（MLN）中积聚所必需的。我们证明，MLN基质细胞表达对嗜酸性粒细胞迁移和存活很重要的基因，如Ccl-11（嗜酸性粒细胞趋化因子-1）、Ccl7、Ccl9和Cxcl2，并且由于新生期LTβR阻断，这些基因中的大多数表达下调。我们还发现，新生期LTβR信号传导是成年MLN中产生轮状病毒特异性IgA抗体反应所必需的，但嗜酸性粒细胞对此反应并非必需。总的来说，我们的研究揭示了新生期LTβR信号传导在调节成年MLN中嗜酸性粒细胞数量方面的作用。
