Lack of Retinoic Acid Leads to Increased Langerin-Expressing Dendritic Cells in Gut-Associated Lymphoid Tissues
Lack of Retinoic Acid Leads to Increased Langerin-Expressing Dendritic Cells in Gut-Associated Lymphoid Tissues
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DOI：
10.1053/j.gastro.2009.11.006
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发表时间：
2010-04-01
期刊：
影响因子：
29.4
通讯作者：
Kweon, Mi-Na
中科院分区：
文献类型：
--
作者：
Chang, Sun-Young;Cha, Hye-Ran;Kweon, Mi-Na
背景与目的：视黄酸（RA）是维持肠道内稳态的关键因子，包括淋巴细胞归巢、免疫球蛋白（IG）A产生以及T调节细胞（Treg）和T辅助细胞17（T（H）17）产生。迄今为止，大多数的注意力集中在树突状细胞（DCs）通过RA启动包括T和B淋巴细胞在内的适应性免疫的功能上。为探讨维甲酸对肠道相关淋巴组织（GALT）DC的影响，我们分析了维生素A缺乏（VAD）小鼠GALT DC亚群的表型和功能。方法：VAD小鼠通过从妊娠第10-14天喂养VAD饮食超过12周来制备。研究结果：在此，我们报道了依赖于CCR 7信号转导的VAD小鼠肠系膜淋巴结（MLN）和肠固有层中langerin（+）DC的大量增加。Langerin（+）DCs的表型与骨髓来源的真皮Langerin（+）DCs比表皮Langerhans细胞更相似。此外，RA受体拮抗剂增强了小鼠和人骨髓和外周血前体细胞的langerin（+）DC的分化。兰杰林（+）DC高度分化，但比VAD小鼠MLN的兰杰林（-）DC炎症性更低。此外，通过消耗VAD小鼠中的langerin（+）DCs，完全消除了对口服递送抗原的耐受性。结论：这些结果表明，Langerin（+）DCs在GALT中的产生受到RA的严格调控，并且组织的微环境决定了DCs的表型。
BACKGROUND & AIMS: Retinoic acid (RA) is a crucial factor for maintaining homeostasis in the gut, including lymphocyte homing, immunoglobulin (Ig) A production, and T regulatory cells (Treg) and T helper cell 17 (T(H)17) generation. Until now, most attention has focused on the function of dendritic cells (DCs) to initiate adaptive immunity including T and B lymphocytes through RA. To investigate the effects of RA on DCs of gut-associated lymphoid tissue (GALT), we analyzed the phenotype and function of DC subsets from GALT of vitamin A-deficient (VAD) mice. METHOD: VAD mice were prepared by feeding them a VAD diet over 12 weeks from gestational days 10-14. RESULTS: Here, we report that tremendous increase of langerin(+) DCs occurred in the mesenteric lymph nodes (MLNs) and gut lamina propria of VAD mice dependent on CCR7 signaling. Langerin(+) DCs have phenotypes more similar to those of bone marrow-derived dermal langerin(+) DCs than epidermal Langerhans cells. Moreover, RA receptor antagonists enhance the differentiation of langerin(+) DCs from mouse and human precursors of bone marrow and peripheral blood. Langerin(+) DCs were highly differentiated but less inflammatory than langerin(-) DCs of MLNs of VAD mice. Moreover, tolerance to orally delivered antigen was completely abrogated by depletion of langerin(+) DCs in the VAD mice. CONCLUSIONS: These results suggest that generation of langerin(+) DCs in the GALT is tightly regulated by RA and that the micro-environment of tissues determines the phenotype of DCs.