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Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance
Mucosal Immunology ( IF 7.9 ) Pub Date : 2021-07-29 , DOI: 10.1038/s41385-021-00434-2
Aiko Ono-Ohmachi 1, 2 , Satoki Yamada 3 , Satoru Uno 3 , Masato Tamai 3 , Kohei Soga 3 , Shotaro Nakamura 3 , Nobuyuki Udagawa 4 , Yuko Nakamichi 5 , Masanori Koide 5 , Yoshikazu Morita 1 , Tomohiro Takano 3 , Takumi Itoh 6, 7 , Shigeru Kakuta 8 , Chikao Morimoto 6 , Shuji Matsuoka 9 , Yoichiro Iwakura 10 , Michio Tomura 11 , Hiroshi Kiyono 12, 13, 14 , Satoshi Hachimura 3 , Haruyo Nakajima-Adachi 3, 12
Affiliation  

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.



中文翻译:

肠系膜淋巴结中的效应记忆 CD4+T 细胞介导食物过敏性肠病模型小鼠的骨丢失,产生 IL-4 优势

肠道炎症可伴有骨质疏松症,但它们之间由免疫反应介导的关系仍不清楚。在这里,我们研究了一种非 IgE 介导的食物过敏性肠病模型,该模型是表达 OVA 特异性 T 细胞受体转基因的卵清蛋白 (OVA) 23-3 小鼠。当给小鼠喂食蛋清 (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增加 CD44 hi CD62L lo CD4 +MLN 和骨髓 (BM) 中的 T 细胞;这些变化因 MLN 而不是脾脏切除而减弱。我们用 EW 饮食喂养 OVA23-3 小鼠的 F1 杂交后代和表达光转换蛋白 KikGR 的小鼠系以追踪 MLN CD4 + T 细胞。光转化的MLN CD44 hi CD62L lo CD4 + T 细胞主要迁移到 BM;凹坑形成试验证明了它们能够通过破骨细胞促进骨损伤。MLN CD44 hi CD62L lo CD4 +中 IL-4 mRNA 的表达显着增加在 EW 喂养的 OVA23-3 小鼠中观察到 T 细胞和骨骼。抗 IL-4 单克隆抗体注射消除了 EW 喂养小鼠原发性炎症期的骨质流失,但在慢性期则较少。这份新报告显示了食物过敏性肠病中 MLN 和远处器官骨骼之间通过 Th2 显性 OVA 特异性 T 细胞和 IL-4 产生的特定炎症关系。

更新日期:2021-07-29
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