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首页> 外文期刊>The Journal of Nutritional Biochemistry >Folate deficiency affects dendritic cell function and subsequent T helper cell differentiation
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Folate deficiency affects dendritic cell function and subsequent T helper cell differentiation

机译：叶酸缺乏会影响树突细胞功能和随后的T辅助细胞分化

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摘要

Insufficient folate status may be related to the increasing prevalence of immune- or inflammation-related chronic diseases. To investigate the effects of folate on immune regulation, we examined the impact of folate deficiency (FD) on dendritic cell (DC) maturation and function and, thus, T helper (Th) cells differentiation. First, bone marrow-derived DCs (BMDCs) were generated from BALB/c mice bone marrow cells cultured in folate-containing (F-BMDCs) or folate-deficient (FD-BMDCs) medium. FD-BMDC displayed more immature phenotype including reduced levels of major histocompatibility complex class II (MHC II), co-stimulatory molecules and characteristic of higher endocytic activity. FD-BMDC produced less IL-12p70 and proinflammatory cytokines in response to lipopolysaccharide. This aberrant DC maturation due to FD resulted in reduced BMDC-induced Th cell activity and lower IL-2, IFN gamma, IL-13 and 1L-10 productions. Further in vivo study confirmed significantly lower IFN gamma and IL-10 productions by T cells and showed higher splenic na ve Th and lower memory T, effector T and regulatory T cell (Treg) percentages in mice fed with the FD diet for 13 weeks. To investigate the role of DCs on T cell activity, splenic DCs (spDC) from FD mice were cocultured with Th cells. The FD spDC had lower MHC II and CD80 expressions and subsequently impaired DC-induced Th differentiation, shown as decreased cytokine productions. This study demonstrated that folate deficiency impaired DC functions and, thus, Th differentiation and responses, suggesting that folate plays a crucial role in maintaining Th cells homeostasis. (C) 2016 Elsevier Inc. All rights reserved.
机译：叶酸状态不足可能与免疫或炎症相关慢性病的发病率增加有关。为了研究叶酸对免疫调节的影响，我们研究了叶酸缺乏（FD）对树突状细胞（DC）成熟和功能以及辅助性T细胞（Th）分化的影响。首先，在含叶酸（F-BMDC）或叶酸缺乏（FD-BMDC）培养基中培养的BALB/c小鼠骨髓细胞产生骨髓源性DC（BMDC）。FD-BMDC表现出更不成熟的表型，包括主要组织相容性复合物II类（MHC II）水平降低、共刺激分子和更高的内吞活性。FD-BMDC对脂多糖的反应是产生较少的IL-12p70和促炎细胞因子。FD导致的DC异常成熟导致BMDC诱导的Th细胞活性降低，IL-2、IFN-γ、IL-13和1L-10的产生降低。进一步的体内研究证实，在喂食FD饮食13周的小鼠中，T细胞产生的IFN-γ和IL-10显著降低，脾脏Nave Th升高，记忆T、效应T和调节性T细胞（Treg）百分比降低。为了研究树突状细胞对T细胞活性的作用，将来自FD小鼠的脾树突状细胞（spDC）与Th细胞共培养。FD-spDC具有较低的MHC II和CD80表达，随后损害DC诱导的Th分化，表现为细胞因子产生减少。这项研究表明，叶酸缺乏会损害DC功能，从而影响Th的分化和反应，这表明叶酸在维持Th细胞内环境稳定中起着至关重要的作用。（C） 2016爱思唯尔公司版权所有。

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