Functional Activity of Th-17 Lymphocytes in Pulmonary Tuberculosis

Кононова, Т. Е.; Уразова, О. И.; Новицкий, В. В.; Чурина, Е. Г.; Kolobovnikova, Yu. V.; Игнатов, М. В.; Zakharova, P. A.; Pechenova, O. V.

doi:10.1007/s10517-014-2438-8

Cited by 15 publications

(14 citation statements)

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“…Although the role of Th17 cells has been investigated in several lung diseases, such as asthma [14], tuberculosis [15], lung cancer [16], and chronic obstructive pulmonary disease [17], there are few data about the peripheral frequency of Th17 cells in ARDS patients. In our study, we found that ARDS patients exhibited a significant increase in the frequency of Th17 cells and their signature cytokine, IL-17, compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to their effector function in defense against extracellular pathogens, T helper (Th)17 cells can promote many autoimmune inflammatory conditions including several lung diseases (asthma [14], tuberculosis [15], lung cancer [16], and chronic obstructive pulmonary disease [17]), unless they are efficiently controlled by regulatory cells [13]. Remarkably, Th17 development relies on the key cytokine TGF-β1, which is also linked to Treg cell development and function, indicating that Th17 and Treg not only exert opposite functions in the immune response but also share reciprocal development pathways.…”

Section: Introductionmentioning

confidence: 99%

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The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome

et al. 2015

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IntroductionRecent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS.MethodsThis prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment.ResultsWithin 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO2/FiO2. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001).ConclusionsThe Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome

et al. 2015

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“…In this study, we found that plasma IL-17 level was increased in AFB-positive patients, but obviously decreased after smear conversion. IL-17 is a proinflammatory cytokine mainly produced by Th17 lymphocytes, which play an immunoregulatory role by producing a unique spectrum of pro-inflammatory cytokines IL-17A, IL-17F, IL-22, IL-26, and IFN-γ [ 11 ]. These cytokines could induce the activation and recruitment of neutrophils, macrophages, and Th1 lymphocytes into the site of infection, which contributed to delimitation of the damaged area in the lung tissue, as well as the inhibition of MTB growth [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that IL-17 plays an important role in the initial immune responses and is involved in both immune protection and immune pathology in MTB infection [ 2 , 9 , 10 ]. The Th17-response is also considered to be the leading mechanism of protection of bronchoalveolar tract and its barrier maintenance [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Decreased IL-17 during treatment of sputum smear-positive pulmonary tuberculosis due to increased regulatory T cells and IL-10

Cui

Jia

et al. 2016

J Transl Med

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BackgroundTuberculosis (TB) remains a major public health concern worldwide. Previous studies have demonstrated that IL-17 plays an important role in initial immune response and is involved in both immune-mediated protection and pathology following infection with Mycobacterium tuberculosis (MTB). However, the alterations and regulation of plasma IL-17 level during TB treatment remain unclear. Moreover, the cell type responsible for the production of IL-17 in TB patients requires further study.MethodsA total of 20 acid-fast bacilli smear-positive (AFB-positive) pulmonary TB patients and 20 age- and gender-matched healthy volunteers were included in our study. Blood samples were collected in heparinized tubes at the time of diagnosis (AFB-positive group) and 3 weeks after the initiation of therapy, when the sputum smear conversion (AFB-negative group) occurred, followed by symptomatic improvement. IL-17 levels and IL-17-producing cells in PBMCs were detected. Lymphocyte populations in the peripheral blood between the AFB-positive and AFB-negative groups were compared by flow-cytometry. A549 cells, a cell line of alveolar epithelial cells, were applied to determine the extent of the pathological damage mediated by IL-17 following MTB infection. Recombinant human IL-10 was used to investigate the regulation of IL-17 expression after sputum smear conversion in AFB-positive pulmonary TB patients.ResultsPlasma IL-17 level were elevated in patients with sputum AFB-positive pulmonary TB, but substantially decreased after TB treatment and smear conversion. Our data indicate that NKT-like cells might be the main source of IL-17, in addition to conventional T cells in AFB-positive pulmonary TB patients. The secretion of IL-17 may be suppressed by regulatory T (Treg) cells and IL-10 during TB treatment. Moreover, the IL-17 levels were positively correlated to both the C-reactive protein and erythrocyte sedimentation rate. Therefore, IL-17 was capable of alveolar epithelial cell damage following MTB infection.ConclusionThe increase in the frequency of Treg cells and IL-10 levels was associated with a decrease in IL-17 in patients receiving TB treatment. Thus, IL-10 and Tregs may function to inhibit immune-mediated pathology in TB patients.

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“…PTX, pentoxifyllinum; ARDS, acute respiratory distress syndrome;.IL, interleukin; TGF, transforming growth factor. A B elusive, they have been investigated in several types of lung disease (18)(19)(20). Recently, Yu et al (21) showed that ARDS patients exhibited a significant increase in the frequency of Th17 cells and their signature cytokine, IL-17.…”

Section: Discussionmentioning

confidence: 99%

Resolution acute respiratory distress syndrome through reversing the imbalance of Treg/Th17 by targeting the cAMP signaling pathway

Sun

et al. 2016

Molecular Medicine Reports

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Acute respiratory distress syndrome (ARDS) is a severe cause of respiratory failure with a mortality rate as high as 40‑46% and without any effective pharmacological treatment available. The present study provided a novel strategy for the treatment of ARDS by specifically interfering with cyclic adenosine monophosphate (cAMP) signaling. Pre-treatment with the phosphodiesterase antagonist pentoxifyllinum (PTX) obviously attenuated lung injury and reduced the mortality of mice with cecal ligature and puncture (CLP)‑induced ARDS, while raising cAMP levels. In addition, pre‑treatment with PTX attenuated CLP‑induced increases in the number of T‑regulatory cells (Tregs) and interleukin (IL)‑17‑producing T‑helper lymphocytes (Th17) among spleen lymphocytes, while partially restoring the Treg/Th17 ratio. Correspondingly, CLP‑induced increases in the secretion of IL‑2, IL‑6, IL‑10 and IL‑17 were attenuated. Furthermore, CLP‑induced increases in forkhead box p3 and RAR‑related orphan receptor γt (RORγt) expression as well as signal transducer and activator of transcription (STAT3) activation were attenuated by PTX. The results indicated that PTX‑induced increases in cAMP may have partly restored the Treg/Th17 balance by modulating the transcription of Foxp3 and RORγt through the STAT3 pathway. In conclusion, the present study provided a novel treatment strategy for ARDS by modulating the balance of Treg/Th17 and the subsequent immune response via cAMP signaling, which requires pre-clinical and clinical validation.

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Functional Activity of Th-17 Lymphocytes in Pulmonary Tuberculosis

Cited by 15 publications

References 5 publications

The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome

The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome

Decreased IL-17 during treatment of sputum smear-positive pulmonary tuberculosis due to increased regulatory T cells and IL-10

Resolution acute respiratory distress syndrome through reversing the imbalance of Treg/Th17 by targeting the cAMP signaling pathway

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