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"Child`s Health" Том 16, №2, 2021

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The significance of αβ Т cells in the development of metainflammation of the adipose tissue in obesity

Authors: Абатуров О.Є., Нікуліна А.O.
Дніпровський державний медичний університет, м. Дніпро, Україна

Categories: Pediatrics/Neonatology

Sections: Specialist manual

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Summary

У літературному огляді наведені сучасні уявлення стосовно ролі αβТ-клітин, які представлені основними групами: CD4+-, CD8+Т-лімфоцитами та двічі негативними CD4–CD8–-Т- і двічі позитивними CD4+CD8+-Т-клітинами адаптивної імунної системи організму, у розвитку метазапалення жирової тканини при ожирінні. Відповідно до сучасної концепції ожиріння асоціюється з гіпертрофією адипоцитів, порушенням адипогенезу, розвитком метазапалення жирової тканини, що відрізняється в ранній адаптивній фазі швидкою реактивацією Т-клітин пам’яті. Фізичний зв’язок клітин, що виконують функцію накопичення енергії, із клітинами імунологічної пам’яті являє собою особливий механізм виживання організму в періоди дефіциту харчування. Надлишок жирової тканини і поява прозапальних гіпертрофованих адипоцитів змінюють спектр і співвідношення продукованих адипокінів і цитокінів, що призводить до рекрутування й активації прозапальних імуноцитів і виснаження пулу протизапальних клітин вродженої й адаптивної імунної системи в жировій тканині. Зміни представництва резидентних рекрутованих імунних клітин, у жировій тканині під час ожиріння характеризуються акумуляцією прозапальних клітин (нейтрофіли, M1-Mϕ, тучні, NK-, ­Th1-, ­Th17-, Th22-клітини) і виснаженням регуляторних і протизапальних популяцій (еозинофіли, M2-Mϕ, ICL2, iNKT, γδT-, ­Th2-, Treg-, B1-клітини). Надлишкова продукція IFN-γ і TNF-α призводить до розвитку інсулінорезистентності, а IL-17 — до деградації екстрацелюлярного матриксу жирової тканини і порушення адипогенезу. При ожирінні CD8+-Т-клітини і M1-Mϕ елімінують гіпертрофовані адипоцити. Зниження активності Treg-клітин збільшує прозапальний потенціал жирової тканини. Незважаючи на досягнуті успіхи в розкритті ролі адаптивної імунної системи при розвитку ожиріння, до сьогодні не ідентифіковані асоційовані з ожирінням антигени жирової тканини, механізми їх генерації, не визначена роль більшості тканиноспецифічних алармінів; не відомі механізми, що визначають час, послідовність й активність рекрутування різних типів імуноцитів. Наведені дані сучасних досліджень імунопатогенезу метазапалення жирової тканини і створення лікарських засобів, що дозволять підвищити ефективність й індивідуалізувати протизапальну терапію у хворих з ожирінням.

The literature review presents modern ideas about the role of αβ T cells, which are represented by the main groups: CD4+, CD8+ T lymphocytes and double-negative CD4–CD8– T and double-positive CD4+CD8+ T cells of the adaptive immune system of the organism in the development of metainflammation of adipose tissue in obesity. According to the modern concept, obesity is associated with adipocyte hypertrophy, impaired adipogenesis, the development of metainflammation of adipose tissue that in the early adaptive phase is characterized by the rapid reactivation of memory T cells. The physical connection of cells performing the function of energy storage with immunological memory cells is a special mechanism for the body’s survival during periods of nutritional deficiency. Excess adipose tissue and the appearance of pro-inflammatory hypertrophied adipocytes change the spectrum and ratio of produced adipokines and cytokines, which leads to the recruitment and activation of pro-inflammatory immunocytes and depletion of the pool of anti-inflammatory cells of the innate and adaptive immune system in adipose tissue. Changes in the representation of resident recruited immune cells in adipose tissue during obesity is characterized by the accumulation of pro-inflammatory cells (neutrophils, M1 Mϕ, mast cells, NK, Th1, Th17, Th22 cells) and depletion of regulatory and anti-inflammatory populations (eosinophils, M2 Mϕ, ILC2, iNKT, γδ T, Th2, Treg, B1 cells). Excessive production of interferon γ and tumor necrosis factor α leads to the development of insulin resistance, and interleukin 17 — to degradation of the extracellular matrix of adipose tissue and impaired adipogenesis. In obesity, CD8+ T cells and M1 Mϕ macrophages eliminate hypertrophied adipocytes. A decrease in the activity of Treg cells increases the pro-inflammatory potential of adipose tissue. Despite the progress achieved in disclosing the role of the adaptive immune system in the development of obesity, the antigens associated with adipose tissue, the mechanisms of their generation have not been identified so far, the role of most tissue-specific alarmins has not been determined; the mechanisms that determine the timing, sequence and activity of recruitment of various types of immunocytes are not known. The data of mo­dern studies on the immunopathogenesis of metainflammation of adipose tissue and the creation of drugs that will improve the efficiency and individualize anti-inflammatory therapy in obese patients are presented.


Keywords

адаптивна імунна система; Т-лімфоцити; метазапалення; ожиріння; діти

adaptive immune system; T-lymphocytes; metainflammation; obesity; children


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