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

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. The purpose 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. Material and methods. 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. Results. 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. Conclusion. 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.