Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance
Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance
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DOI：
10.1038/s41385-021-00434-2
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发表时间：
2021-07-29
影响因子：
8
通讯作者：
Nakajima-Adachi，Haruyo
中科院分区：
文献类型：
--
作者：
Ono-Ohmachi，Aiko;Yamada，Satoki;Nakajima-Adachi，Haruyo
肠道炎症可能伴随骨质疏松症，但它们之间由免疫反应介导的关系仍不清楚。在这里，我们研究了表达 OVA 特异性 T 细胞受体转基因的卵清蛋白 (OVA) 23-3 小鼠的非 IgE 介导的食物过敏性肠病模型。当给小鼠喂蛋清（EW）饮食时，肠系膜淋巴结（MLN）及其致病性 CD4+T 细胞对肠病的发生和恶化很重要。 EW 喂养的 OVA23-3 小鼠也出现骨质流失，并且 MLN 和骨髓 (BM) 中的 CD44hiCD62LloCD4+T 细胞增加；这些变化可以通过 MLN 减弱，但不能通过脾切除减弱。我们给 OVA23-3 小鼠和表达光转换蛋白 KikGR 的小鼠品系的 F1 杂交后代喂食 EW 饮食，以追踪 MLN CD4+T 细胞。光转化的 MLN CD44hiCD62LloCD4+T 细胞主要迁移至 BM；凹坑形成实验证明了它们通过破骨细胞促进骨损伤的能力。在 EW 喂养的 OVA23-3 小鼠中观察到 MLN CD44hiCD62LloCD4+T 细胞和骨中 IL-4 mRNA 的表达显着增加。在EW喂养的小鼠中，注射抗IL-4单克隆抗体可以消除原发炎症阶段的骨质流失，但在慢性阶段则效果较差。这份新颖的报告显示了食物过敏性肠病中 MLN 和骨骼（远处器官）之间通过 Th2 主导型 OVA 特异性 T 细胞和 IL-4 产生的特定炎症关系。
Intestinal inflammation can be accompanied by osteoporosis, but their relationship, mediated by immune responses, remains unclear. Here, we investigated a non-IgE-mediated food-allergic enteropathy model of ovalbumin (OVA) 23-3 mice expressing OVA-specific T-cell-receptor transgenes. Mesenteric lymph nodes (MLNs) and their pathogenic CD4+T cells were important to enteropathy occurrence and exacerbation when the mice were fed an egg-white (EW) diet. EW-fed OVA23-3 mice also developed bone loss and increased CD44hiCD62LloCD4+T cells in the MLNs and bone marrow (BM); these changes were attenuated by MLN, but not spleen, resection. We fed an EW diet to F1 cross offspring from OVA23-3 mice and a mouse line expressing the photoconvertible protein KikGR to track MLN CD4+T cells. Photoconverted MLN CD44hiCD62LloCD4+T cells migrated predominantly to the BM; pit formation assay proved their ability to promote bone damage via osteoclasts. Significantly greater expression of IL-4 mRNA in MLN CD44hiCD62LloCD4+T cells and bone was observed in EW-fed OVA23-3 mice. Anti-IL-4 monoclonal antibody injection canceled bone loss in the primary inflammation phase in EW-fed mice, but less so in the chronic phase. This novel report shows the specific inflammatory relationship, via Th2-dominant-OVA-specific T cells and IL-4 production, between MLNs and bone, a distant organ, in food-allergic enteropathy.