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鼠李糖乳杆菌和德氏乳杆菌对苍耳烷诱导狼疮模型调节性 T 细胞的改善作用。

Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane-induced lupus mice model.

机构信息

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Cell Physiol. 2019 Jun;234(6):9778-9786. doi: 10.1002/jcp.27663. Epub 2018 Oct 28.

Abstract

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane-induced lupus mice model. Fifty-four female BALB/c mice (3-5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE-induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble-stranded DNA (anti-dsDNA), antiribonucleoprotein (anti-RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL-6), IL-10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti-dsDNA, and anti-RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti-dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL-6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE-induced mice.

摘要

调节性 T 细胞(Tregs)在控制免疫反应和诱导外周耐受方面发挥着不可或缺的作用。Tregs 的失调参与了系统性红斑狼疮(SLE)的发病机制。耐受原性益生菌已显示出在控制自身免疫性疾病方面的有益效果。我们评估了德氏乳杆菌和鼠李糖乳杆菌对 Pristane 诱导的狼疮小鼠模型中 Tregs 及其相关分子的预防和治疗作用。54 只雌性 BALB/c 小鼠(3-5 周龄)被随机分为九组。所有组均使用 Pristane 诱导狼疮。预防组从第 0 天(注射 Pristane 时)开始治疗,治疗组在 2 个月后用鼠李糖乳杆菌、德氏乳杆菌、两种益生菌的混合物和泼尼松龙治疗。一组被认为是没有任何治疗的 SLE 诱导对照组。检测抗核抗体(ANA)、抗双链 DNA(抗-dsDNA)、抗核糖核蛋白(抗-RNP)、蛋白尿、血清肌酐、尿素水平、叉头框 P3(Foxp3)、白细胞介素 6(IL-6)、IL-10、转化生长因子β的表达以及 Tregs 的数量。Pristane 诱导的 SLE 导致脂肉芽肿的形成、ANA、抗-dsDNA 和抗-RNP 的出现。益生菌的摄入降低了脂肉芽肿、ANA 和抗-dsDNA 的水平。此外,在接受益生菌的组中,Tregs 和 Foxp3 的表达水平增加,而 IL-6 减少。预防组益生菌的作用更为显著。这些结果可能表明德氏乳杆菌和鼠李糖乳杆菌在增强 Tregs、减少炎症细胞因子和 SLE 诱导小鼠疾病严重程度方面的有效性。

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