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[微生物群和类黄酮在维持与肠道免疫屏障相关的辅助性和调节性T淋巴细胞平衡中的作用]

[The role of microbiota and flavonoids in maintaining the balance of helper and regulatory T-lymphocytes associated with the intestinal immune barrier].

作者信息

Pavlova S I

机构信息

Chuvash State University named after I.N. Ulyanov, 428015, Cheboksary, Russian Federation.

出版信息

Vopr Pitan. 2024;93(1):22-32. doi: 10.33029/0042-8833-2024-93-1-22-32. Epub 2024 Jan 19.

Abstract

The gastrointestinal tract is a barrier, represented by dynamic and mutually regulating components (microbial, chemical, physical and immune) for the selective penetration of luminal contents into the internal environment. From the point of view of immunologists, even in a physiological condition, the epithelium of the intestinal wall is in a state of mild inflammation, which is explained by the constant invasion of antigens (food, microbial) and, in turn, the constant readiness of the immune system to respond. of this review was to analyze information about the formation of microbial and immunological barriers, immunological tolerance to microbiota and the possible role of flavonoids in this. . The literature search was carried out using PubMed, ResearchGate, Elibrary databases mainly for the last 10 years, using the following keywords: flavonoid, gut microbiome/microbiota, Th17, Treg, RORγt, immunity, segmented filamentous bacteria. . During the immune response, a significant role in maintaining the intestinal barrier function is assigned to helper T lymphocytes type 17 (Th17). The intestinal microbiome is a key element in the formation of the immune barrier. Th17 differentiation in the intestine is fully triggered by commensals (apparently, the main role belongs to segmented filamentous bacteria) after weaning and the start of complementary feeding. Pro-inflammatory Th17 effectors in the gut are controlled by anti-inflammatory regulatory T-cells (Treg). In recent years, it has been established that despite the opposing functions of regulatory cells and effector Th17 cells, their differentiation is similar and is characterized by the expression of the common transcription factor RORγt. The main part of the peripheral regulatory lymphocytes of the intestine is a population that stably expresses not only FOXP3, but also RORγt. Flavonoids, which are plant secondary metabolites of the polyphenolic structure, are able to inhibit intracellular kinases and, as a result, influence the activation and implementation of effector functions of immunocompetent cells. Some flavonoids promote RORγt expression and appear to be able to reprogram the effector phenotype of Th17 cells, reducing their pathogenicity. . Understanding the interactions between the microbiota, immune cells, and factors involved in their regulation, which are critical for the maintenance of tolerance, may facilitate progress in the prevention and therapeutic approaches to treat immunoinflammatory and autoimmune diseases.

摘要

胃肠道是一道屏障,由动态且相互调节的成分(微生物、化学、物理和免疫成分)构成,用于管腔内容物选择性地渗透进入内环境。从免疫学家的角度来看,即使在生理状态下,肠壁上皮也处于轻度炎症状态,这是由于抗原(食物、微生物)的持续侵入,以及免疫系统相应的持续准备状态所致。本综述的目的是分析有关微生物和免疫屏障形成、对微生物群的免疫耐受以及黄酮类化合物在此过程中可能作用的信息。文献检索主要使用PubMed、ResearchGate、Elibrary数据库,检索过去10年的文献,使用的关键词如下:黄酮类化合物、肠道微生物群/微生物、辅助性T细胞17(Th17)、调节性T细胞(Treg)、维甲酸相关孤儿受体γt(RORγt)、免疫、分节丝状菌。在免疫反应过程中,17型辅助性T淋巴细胞(Th17)在维持肠道屏障功能中发挥重要作用。肠道微生物群是免疫屏障形成的关键要素。断奶和开始添加辅食后,共生菌(显然,主要作用属于分节丝状菌)能充分触发肠道内Th17的分化。肠道内促炎性的Th17效应细胞受抗炎性调节性T细胞(Treg)控制。近年来已证实,尽管调节性细胞和效应性Th17细胞功能相反,但其分化相似,且以共同转录因子RORγt的表达为特征。肠道外周调节性淋巴细胞的主要部分是一个不仅稳定表达叉头框蛋白3(FOXP3),还表达RORγt的群体。黄酮类化合物是具有多酚结构的植物次生代谢产物,能够抑制细胞内激酶,从而影响免疫活性细胞效应功能的激活和发挥。一些黄酮类化合物促进RORγt表达,似乎能够重新编程Th17细胞的效应表型,降低其致病性。了解微生物群、免疫细胞及其调节相关因素之间的相互作用,这对维持耐受性至关重要,可能有助于推进免疫炎症和自身免疫性疾病的预防和治疗方法。

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