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

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Karolina A. Sidletskaya ◽  
Tatyana I. Vitkina ◽  
Yulia K. Denisenko ◽  
Elena E. Mineeva

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.

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Elena P. Kalinina ◽  
Yulia K. Denisenko ◽  
Tatyana I. Vitkina ◽  
Elena G. Lobanova ◽  
Tatyana P. Novgorodtseva ◽  
...  

Background. Comorbidity of chronic obstructive pulmonary disease (COPD) and asthma (asthma COPD overlap syndrome, ACOS) is a significant problem in pulmonary practice, whose pathogenetic issues are not clarified yet.Objective. To study the features of the regulation of immune response in patients with comorbid COPD and asthma.Methods. We assessed the levels of CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, HLA-DR, total IgE, TNF-α, IL-4, IFN-γ, TXB2, and LTB4in patients with comorbid COPD and asthma.Results. The study involved 44 people with COPD, 39 people with asthma, and 12 people with comorbid COPD and asthma. The specific features in comorbid COPD and asthma were lymphocytosis, increased absolute count of T-helper cells, increased cytotoxic T-lymphocytes in relative and absolute count, increased relative and absolute numbers of B-lymphocytes, and high levels of total IgE. The elevated levels of TNF-αand IL-4 and inhibition of IFN-γproduction were detected. The content of LTB4was maximal; TXB2levels were higher than in control group but lower than in COPD and asthma.Conclusion. In comorbid COPD and asthma inflammation increased even during stable period. High levels of eicosanoids, low production of Th1-type cytokines, and active synthesis of opposition IL-4, along with increased IgE, indicate the activation of Th2-type immune response.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1205
Author(s):  
Małgorzata Sobstyl ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Rafał Hrynkiewicz ◽  
Dominika Bębnowska ◽  
Izabela Korona-Głowniak ◽  
...  

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.


Parasitology ◽  
2016 ◽  
Vol 143 (5) ◽  
pp. 606-616 ◽  
Author(s):  
ADRIANA AGUADO-MARTÍNEZ ◽  
AFONSO P. BASTO ◽  
JOACHIM MÜLLER ◽  
VRENI BALMER ◽  
VERA MANSER ◽  
...  

SUMMARYImmunoprophylactic products against neosporosis during pregnancy should induce an appropriately balanced immune response. In this respect, OprI, a bacterial lipoprotein targeting toll like receptor (TLR)2, provides promising adjuvant properties. We report on the manipulation of the innate and the T-cell immune response through the fusion of OprI with the Neospora caninum chimeric protein Mic3-1-R. In contrast to Mic3-1-R, OprI-MIC3-1-R significantly activated bone-marrow dendritic cells from naïve mice. Mice immunized with OprI-Mic3-1-R induced an immune response with mixed T helper (Th)1 and Th2 properties (high levels of both immunoglobulin (Ig)G1 and IgG2a and of interleukin (IL)-10, IL-12(p70) and interferon-γ responses) whereas Mic3-1-R+saponin induced a clear Th2-biased response (low IgG2a and high IL-4 and IL-10). After mating and challenge with N. caninum, increased expression of interferon-γ was only found in placentas from OprI-Mic3-1-R immunized dams. However, no protection against vertical transmission and neonatal mortality was observed in either of the two groups. These results indicated that more exhaustive studies must be done to elucidate the immune mechanisms associated with transplacental transmission. Antigen linkage to TLR2-ligands, such as OprI, is a useful tool to investigate this enigma by reorienting the innate and adaptive immune responses against other candidate antigens in future studies.


2018 ◽  
Vol 20 (6) ◽  
pp. 855-864 ◽  
Author(s):  
E. P. Kalinina ◽  
T. I. Vitkina ◽  
V. V. Knyshova ◽  
E. A. Fedoseeva ◽  
T. P. Novgorodtseva ◽  
...  

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.


Lung ◽  
2009 ◽  
Vol 187 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Stefan Pabst ◽  
Vildan Yenice ◽  
Martina Lennarz ◽  
Izabela Tuleta ◽  
Georg Nickenig ◽  
...  

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