Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease

Objective. According to modern views, the differences in the clinical course of chronic obstructive pulmonary disease (COPD) are associated with certain types of T-helper (Th) immune response. Recent data have shown that toll-like receptor 2 (TLR2) is involved in the development of Th immune respons...

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Main Authors: Karolina A. Sidletskaya, Tatyana I. Vitkina, Yulia K. Denisenko, Elena E. Mineeva
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Canadian Respiratory Journal
Online Access:http://dx.doi.org/10.1155/2021/5596095
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author Karolina A. Sidletskaya
Tatyana I. Vitkina
Yulia K. Denisenko
Elena E. Mineeva
author_facet Karolina A. Sidletskaya
Tatyana I. Vitkina
Yulia K. Denisenko
Elena E. Mineeva
author_sort Karolina A. Sidletskaya
collection DOAJ
description Objective. According to modern views, the differences in the clinical course of chronic obstructive pulmonary disease (COPD) are associated with certain types of T-helper (Th) immune response. Recent data have shown that toll-like receptor 2 (TLR2) is involved in the development of Th immune response. However, TLR2-mediated regulation of Th subpopulation balance in COPD needs to be elucidated. The aim of our work is to determine the mechanisms of TLR2-mediated regulation of Th immune response in COPD of varying severity. Methods. The study included 323 smokers/ex-smokers with stable COPD (GOLD I, GOLD II, and GOLD III) and 97 healthy nonsmokers (control group). Serum levels of Th1 (TNF-α and IFN-γ), Th2 (IL-4), Th17 (IL-6 and IL-17A), Treg (IL-10) cytokines, and the percentage of peripheral blood Th cells expressing TLR2 (CD4+CD282+) were assessed by flow cytometry. Serum concentrations of IL-21 (Th17) and TGF-β1 (Treg) were measured using the ELISA method. The predominant Th cytokine profile in serum was determined by calculating the ratios between levels of Th1 and Th17 cytokines. Spearman’s correlation test was performed. Results. Patients with COPD GOLD II and III with Th1 and Th17 cytokine profiles exhibited an increase in the percentage of CD4+CD282+ cells compared to the control group. In COPD GOLD I–III, positive correlations between CD4+CD282+ cell frequency and Th17 cytokine levels (IL-6, IL-17A, and IL-21) were found. In COPD GOLD I, IL-10 concentration was negatively correlated with the percentages of studied cells; in COPD GOLD II, a positive correlation between these parameters was noted. Conclusions. Enhanced TLR2 expression on CD4+ cells shifts cytokine profile toward Th17 phenotype that plays a crucial role in COPD progression. The level of TLR2 expression on peripheral blood CD4+ cells may be considered as a biomarker for diagnosing and predicting the progression of COPD.
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spelling doaj-art-22f04bdeec8e43cfbb5b25062aa41a052025-02-03T06:12:56ZengWileyCanadian Respiratory Journal1198-22411916-72452021-01-01202110.1155/2021/55960955596095Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary DiseaseKarolina A. Sidletskaya0Tatyana I. Vitkina1Yulia K. Denisenko2Elena E. Mineeva3Vladivostok Branch of Federal State Budgetary Science Institution “Far Eastern Scientific Center of Physiology and Pathology of Respiration”–Institute of Medical Climatology and Rehabilitative Treatment, Russian Street 73-g, Vladivostok 690105, RussiaVladivostok Branch of Federal State Budgetary Science Institution “Far Eastern Scientific Center of Physiology and Pathology of Respiration”–Institute of Medical Climatology and Rehabilitative Treatment, Russian Street 73-g, Vladivostok 690105, RussiaVladivostok Branch of Federal State Budgetary Science Institution “Far Eastern Scientific Center of Physiology and Pathology of Respiration”–Institute of Medical Climatology and Rehabilitative Treatment, Russian Street 73-g, Vladivostok 690105, RussiaVladivostok Branch of Federal State Budgetary Science Institution “Far Eastern Scientific Center of Physiology and Pathology of Respiration”–Institute of Medical Climatology and Rehabilitative Treatment, Russian Street 73-g, Vladivostok 690105, RussiaObjective. According to modern views, the differences in the clinical course of chronic obstructive pulmonary disease (COPD) are associated with certain types of T-helper (Th) immune response. Recent data have shown that toll-like receptor 2 (TLR2) is involved in the development of Th immune response. However, TLR2-mediated regulation of Th subpopulation balance in COPD needs to be elucidated. The aim of our work is to determine the mechanisms of TLR2-mediated regulation of Th immune response in COPD of varying severity. Methods. The study included 323 smokers/ex-smokers with stable COPD (GOLD I, GOLD II, and GOLD III) and 97 healthy nonsmokers (control group). Serum levels of Th1 (TNF-α and IFN-γ), Th2 (IL-4), Th17 (IL-6 and IL-17A), Treg (IL-10) cytokines, and the percentage of peripheral blood Th cells expressing TLR2 (CD4+CD282+) were assessed by flow cytometry. Serum concentrations of IL-21 (Th17) and TGF-β1 (Treg) were measured using the ELISA method. The predominant Th cytokine profile in serum was determined by calculating the ratios between levels of Th1 and Th17 cytokines. Spearman’s correlation test was performed. Results. Patients with COPD GOLD II and III with Th1 and Th17 cytokine profiles exhibited an increase in the percentage of CD4+CD282+ cells compared to the control group. In COPD GOLD I–III, positive correlations between CD4+CD282+ cell frequency and Th17 cytokine levels (IL-6, IL-17A, and IL-21) were found. In COPD GOLD I, IL-10 concentration was negatively correlated with the percentages of studied cells; in COPD GOLD II, a positive correlation between these parameters was noted. Conclusions. Enhanced TLR2 expression on CD4+ cells shifts cytokine profile toward Th17 phenotype that plays a crucial role in COPD progression. The level of TLR2 expression on peripheral blood CD4+ cells may be considered as a biomarker for diagnosing and predicting the progression of COPD.http://dx.doi.org/10.1155/2021/5596095
spellingShingle Karolina A. Sidletskaya
Tatyana I. Vitkina
Yulia K. Denisenko
Elena E. Mineeva
Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease
Canadian Respiratory Journal
title Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease
title_full Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease
title_fullStr Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease
title_full_unstemmed Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease
title_short Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease
title_sort role of toll like receptor 2 in regulation of t helper immune response in chronic obstructive pulmonary disease
url http://dx.doi.org/10.1155/2021/5596095
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AT yuliakdenisenko roleoftolllikereceptor2inregulationofthelperimmuneresponseinchronicobstructivepulmonarydisease
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