Changes in the Surface Il-6 Receptor Expression of Distinct Immune Cells in Progression of Chronic Obstructive Pulmonary Disease

Виткина, Т. И.; Андреевна, Сидлецкая Каролина; Денисенко, Ю К

doi:10.15789/1563-0625-2017-2-191-196

Cited by 7 publications

(5 citation statements)

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“…In our earlier studies, it has been shown that IL-6R expression on the surface of circulating Th cells increases at last stages of COPD [21], thus indicating the importance of the activation of classical IL-6 signaling in these cells for the inflammatory process development during disease. In this study, we have found that severe COPD development accompanied by the formation of Th17associated cytokine profile is characterized by increase in the IL-6 blood levels and the number of Th cells expressing IL-6R.…”

Section: Discussionmentioning

confidence: 86%

Features of cytokine signaling forming T-helper immune response in COPD of varying severity

Виткина¹,

Sidletskaya²

2020

Russ Open Med J

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Introduction — Currently, chronic obstructive pulmonary disease (COPD) is a global public health problem. However, molecular mechanisms of the development of this pathology are still poorly understood. The aim is to establish mechanisms of cytokine regulation of T-helper (Th) immune pathway in patients with COPD of varying severity. Material and Methods — The study included 112 patients with stable COPD (mild, moderate and severe grade) and 32 healthy volunteers (control group). We investigated serum cytokine levels (tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 4 (IL-4), IL-6, IL-10, IL-17A) and the percentage of circulating Th cells (CD4+) expressing membrane receptor to IL-6 (IL-6R or CD126+), using flow cytometry. The levels of transforming growth factor-β1 (TGF-β1) and IL-21 were detected by ELISA. The direction of immune response in COPD patients was determined depending on the prevalence of cytokines playing a crucial role in the formation of certain Th cells type (Th1, Th17). Results — Th1-associated cytokine profile was expressed at the initial stage of COPD; the Th17-associated cytokine profile begins to prevail at severe COPD. Among COPD patients with Th1-associated cytokine profile, a statistically significant increase in the number of CD4+CD126+ cells in comparison with the control group was identified only in severe COPD. In the group of COPD patients with Th17-associated cytokine profile, an increase in the number of CD4+CD126+ cells were observed at all severity stages of the pathology. Conclusion — Moderate and severe COPD are characterized by the predominance of Th17-associated cytokine profile leading to chronic inflammation. The increase in IL-6R expression levels in circulating CD4+ cells serves as the mechanism for enhancing Th17-associated response in COPD.

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Section: Discussionmentioning

confidence: 86%

Features of cytokine signaling forming T-helper immune response in COPD of varying severity

Виткина¹,

Sidletskaya²

2020

Russ Open Med J

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“…В наибольшей степени экспрессия IL-6R возрастает на гранулоцитах (нейтрофилах) и Th-клетках, делая их мишенями для воздействия IL-6 посредством классического сигналинга. Основываясь на результатах исследований последних лет [29, 38,43], мы предполагаем, что классический путь передачи IL-6 сигнала может являться компенсаторным механизмом, направленным на подавление системной воспалительной реакции при ХОБЛ [4,5,7]. В связи с тем, что на всех стадиях ХОБЛ наблюдалась повышенная экспрессия IL-6R на Th-клетках, авторы оценили влияние IL-6 на формирование Т-хелперного иммунного ответа у пациентов с данной патологией.…”

Section: The Review Presents the Known Pathophysiological Mechanisms unclassified

The Role of Interleukin-6 Signaling in Development of Systemic Inflammation in Chronic Obstructive Pulmonary Disease

Виткина¹,

Сидлецкая²,

Sidleckaya³

2018

Bulletin Physiology and Pathology of Respiration

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The review focuses on the role of interleukin-6 (IL-6) signaling in the development of a systemic inflammatory process in chronic obstructive pulmonary disease (COPD). In most researches the attention is paid to local inflammation in COPD. However, it is known that the pathology is characterized by a systemic inflammatory process, which is manifested in the increased levels of proinflammatory mediators in blood flow, and the study of the molecular mechanisms of its development is very important for the therapy of the disease. One of the key mediators of systemic inflammation is cytokine IL-6 which has pro- and antiinflammatory properties. Its effect on the cells is determined by the type of signaling. Nowadays three types of IL-6 signaling are identified: transsignaling, classical and cluster signaling. The review presents the known pathophysiological mechanisms of the development of systemic inflammation in COPD involving IL-6. As a proinflammatory cytokine, IL-6 performs the following functions: transmission of a signal on lung tissue damage, initiation of leukocyte migration into the inflammation site, inhibition of T-cell apoptosis into the inflammation site, influence on T helper differentiation, participation in pathophysiological reactions of development of emphysema and fibrosis. The significance of IL-6 transsignaling for the development of inflammation in COPD has been confirmed by many studies, while there are practically no works devoted to the study of classical IL-6 signaling in COPD. The data presented in the review indicate the need for further study of the role of different types of IL-6 signaling, especially classical signaling, in the regulation of systemic inflammation in COPD.

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“…В последние годы значительный интерес вызывает роль IL-6 в прогрессировании ХОБЛ. Согласно проведенным исследованиям, повышенный системный уровень IL-6 является отличительной чертой ХОБЛ и коррелирует со степенью воспаления нижних дыхательных путей и снижением легочной функции [2,14]. В связи с этим изучение молекулярных механизмов действия IL-6 при ХОБЛ вызывает большой интерес.…”

Section: иммунологические особенности хоблunclassified

“…диагностированы максимальные значения провоспалительных цитокинов IL-17, IL-21 и противовоспалительных -IL-10, TGF-β1, что указывает на продуцирующую активацию Th17-лимфоцитов, играющих роль дирижера воспалительной реакции. У 50% пациентов ( [2,11]. Кроме того, IL-6 способен подавлять апоптоз клеток посредством индукции антиапоптотических регуляторов.…”

Section: результаты и обсуждениеunclassified

CLINICAL AND IMMUNOLOGICAL COMPARISONS IN Th- DEPENDENT IMMUNE RESPONSE MECHANISMS AMONG PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

et al. 2018

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Chronic obstructive pulmonary disease (COPD) is a global public health problem. Studies in immunological features and their correlations with clinical course of COPD are of importance. The aim of this study was to elucidate clinical and immunological features in COPD of different severity grade, concerning Th1- and Тh17-dependent types of immune response.The study included 132 COPD patients and 32 healthy individuals. According to clinical and functional patterns, the patients with COPD were divided into 3 groups, i.e., 36 cases (28%) of mild severity; 62 individuals (48%), of moderate severity, and 30 patients (23%) of severe clinical grade. We have performed both clinical and immunological evaluation of the patients. The Th1- and Th17-specific lymphocyte subpopulations were assessed according to the serum levels of cytokines, i.e. tumor necrosis factor (TNFα), IL-4, IL-10, IL-17A, IL-21, IFNγ, as well as transforming growth factor β1 (TGF-β1). We have also determined expression of IL-6R receptor (CD126+) on mature T lymphocytes (CD3+) and T helper cells (CD4+) from peripheral blood. We have obtained the following results: the patients with mild-grade COPD exhibited three different T cell phenotypes were determined, with a prevalence of Th1-dependent immune response. The IL-6R were mostly expressed on CD3+CD126+ cells for the Th1/Th17 phenotype, and CD4+CD126+ cells in cases of Th17-dependent type immune response. In patients with COPD of moderate severity, the Th1, Th17, or Th1/Th17 types of immune response was revealed at similar rates. The level of IL-6R expression on mature T lymphocytes and T-helper cells increased to the greatest extent in cases of Th17-dependent immune response. In severe COPD patients, we have found a dominance of Th17 and Th1/Th17 type immune response. The levels of IL-6R expressionwere increased in Th17- and Th1/Th17-dependent types of immune response, the most significant increase was observed for CD4+ cells in Th17 phenotype. Clinical features of COPD proved to be associated with the phenotypes of immune response. These results allow of specifying the inflammatory phenotype, predicting the course of chronic disease, and selecting appropriate therapy.

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Changes in the Surface Il-6 Receptor Expression of Distinct Immune Cells in Progression of Chronic Obstructive Pulmonary Disease

Cited by 7 publications

References 7 publications

Features of cytokine signaling forming T-helper immune response in COPD of varying severity

Features of cytokine signaling forming T-helper immune response in COPD of varying severity

The Role of Interleukin-6 Signaling in Development of Systemic Inflammation in Chronic Obstructive Pulmonary Disease

CLINICAL AND IMMUNOLOGICAL COMPARISONS IN Th- DEPENDENT IMMUNE RESPONSE MECHANISMS AMONG PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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