Intracellular mechanisms of Th17/Treg differentiation in mild and moderate COPD patients

Lourenço, Juliana Dias; Silva, Larissa Emidio de França; Genaro, Isabella Santos de; Ito, Juliana Tiyaki; Pietrobon, Anna Julia; Sato, Maria Notomi; Gross, Jefferson Luiz; Negri, Elnara M.; Barbeiro, Denise Frediani; Teodoro, Walcy Rosolia; Miranda, Jurandir Tomaz de; Saraiva-Romanholo, Beatriz Mangueira; Vieira, Rodolfo de Paula; Lopes, Fernanda Degobbi Tenório Quirino dos Santos

doi:10.1183/13993003.congress-2019.pa3340

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“…However, our study included smokers and ex-smokers with COPD, and no patient with the predominant Th2 cytokine profile was identified. Accumulating evidence demonstrated that COPD progression is associated with the development of the Th17 immunoregulatory pathway and imbalance between Th17 and Treg cell subpopulations [ 11 – 13 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

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

Sidletskaya

Виткина

Denisenko

et al. 2021

Canadian Respiratory Journal

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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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