Effect of memory CD4+ T cells’ signal transducer and activator of transcription (STATs) functional shift on cytokine-releasing properties in asthma

Chen, Zhihong; Pan, Jue; Jia, Yi; Li, Dandan; Min, Zhihui; Su, Xiaojie; Yuan, Honglei; Geng, Suxia; Cao, Shengxuan; Zhu, Liangliang; Wang, Xiangdong

doi:10.1007/s10565-016-9357-6

Cited by 9 publications

(10 citation statements)

References 24 publications

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“…Asthma is a chronic inflammatory airway disease, and oxidative stress may be involved in its pathogenesis. Chronic airway inflammation, airway smooth muscle contraction and bronchial hyperreactivity are three major characteristics of the pathogenesis of asthma [ 80 – 82 ]. Considerable evidence has shown that ROS are involved in these three processes.…”

Section: Ros-related Lung Diseasesmentioning

confidence: 99%

The pathophysiological role of mitochondrial oxidative stress in lung diseases

2017

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Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses. In this review, crosstalk among alveolar epithelial cells, alveolar macrophages and mitochondria is examined. ROS-related transcription factors and downstream cell signaling pathways are also discussed. We conclude that targeting oxidative stress with antioxidant agents, such as thiol molecules, polyphenols and superoxide dismutase (SOD), and promoting mitochondrial biogenesis should be considered as novel strategies for treating lung diseases that currently have no effective treatment options.

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Section: Ros-related Lung Diseasesmentioning

confidence: 99%

The pathophysiological role of mitochondrial oxidative stress in lung diseases

2017

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“…In conclusion, IRF1 could be a key gene for glucocorticoids resistance of NA. Signal transducer and activator of transcription 1 (STAT1) regulates production of Th1 cellspecific cytokine to alter inflammatory response and it is a key mediator in IFNγ signaling (Chen et al, 2017;Zhang et al, 2018). Several studies have shown that STAT1 participants in the differentiation of Th17 cells and it may become a key gene in the development of NA (Villarino et al, 2010;Kimura et al, 2008;Nielsen et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis

Chen

Feng

et al. 2022

Front. Mol. Biosci.

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Background: Asthma is a heterogeneous disease with different subtypes including eosinophilic asthma (EA) and neutrophilic asthma (NA). However, the mechanisms underlying the difference between the two subtypes are not fully understood.Methods: Microarray datasets (GSE45111 and GSE137268) were acquired from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in induced sputum between EA (n = 24) and NA (n = 15) were identified by “Limma” package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Gene set enrichment analysis (GSEA) were used to explore potential signaling pathways. Weighted gene co-expression network analysis (WGCNA) were performed to identify the key genes that were strongly associated with EA and NA.Results: A total of 282 DEGs were identified in induced sputum of NA patients compared with EA patients. In GO and KEGG pathway analyses, DEGs were enriched in positive regulation of cytokine production, and cytokine-cytokine receptor interaction. The results of GSEA showed that ribosome, Parkinson’s disease, and oxidative phosphorylation were positively correlated with EA while toll-like receptor signaling pathway, primary immunodeficiency, and NOD-like receptor signaling pathway were positively correlated with NA. Using WGCNA analysis, we identified a set of genes significantly associated NA including IRFG, IRF1, STAT1, IFIH1, IFIT3, GBP1, GBP5, IFIT2, CXCL9, and CXCL11.Conclusion: We identified potential signaling pathways and key genes involved in the pathogenesis of the asthma subsets, especially in neutrophilic asthma.

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“…Исследования, проведенные на взрослых лицах, отмечают повышенное содержание Т-клеток памяти у пациентов с БА в сравнении со здоровыми лицами, которое ассоциировано со степенью тяжести данного заболевания [2]. Также повышение количества Т-клеток памяти связывают с изменением их функциональной активности и существованием различных эндотипов БА [4]. Количество Tnaïve клеток (CD4 + CD45R0и CD8 + CD45R0 -), по данным других авторов, не изменяется при БА, что согласуется с нашим исследованием [2,27].…”

Section: Discussionunclassified

“…По данным литературы, точная роль различных субпопуляций Т-клеток памяти в патогенезе БА не установлена. Так, в проведенном недавно исследовании, наряду с функциональными изменениями Т-клеток памяти, было выявлено повышенное содержание TcmCD62L + и TemCD62L + в CD4 + клетках периферической крови у пациентов с БА [4]. В другой работе было показано, что у взрослых пациентов с БА, вне зависимости от формы и степени тяжести заболевания, повышается число CD4 + Tcm, но не CD4 + Tem по сравнению с донорами, что не подтверждается данными нашего исследования [28].…”

Section: Discussionunclassified

“…Экспериментальные данные свидетельствуют, что резидентные аллергенспецифичные Т-клетки памяти накапливаются в легочной ткани в результате сенсибилизации и могут приводить к развитию БА [11]. Также у пациентов с БА обнаружено повышенное содержание CD4 + T-клеток памяти, которое сопровождается такими функциональными изменениями, как повышенная продукция IL-5, IL-17 и снижение синтеза IFNγ [4].…”

Section: Introductionunclassified

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CONTENTS OF CD4<sup>+</sup> AND CD8<sup>+</sup> EFFECTOR MEMORY CELLS AND PROLIFERATIVE ACTIVITY OF T LYMPHOCYTES IN BRONCHIAL ASTHMA

et al. 2019

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Bronchial asthma is a chronic inflammatory disease of the respiratory tract. T-lymphocytes play a key role in pathogenesis of this allergic disease. The reduction in number of naïve T cells and the accumulation of memory T cells in bronchial asthma are accompanied by dysregulation of T lymphocyte function. In present study, we have investigated the contents of different T lymphocyte subpopulations in peripheral blood as well as in resting and PHA-stimulated cultures, along with their proliferative capacity in patients with bronchial asthma and healthy donors. The study included 10 patients with bronchial asthma (age 45.4±11.8 years). One-half of patients was in remission state, the others having been at the stage of clinical exacerbation. The group of donors was formed by healthy individuals matched by gender and age to the patients. Based on expression of cell surface markers CD45R0, CD62L and CD197 (CCR7), the CD4+ and CD8+T lymphocytes were divided into central (Tcm) and effector memory cells (Tem), naïve T lymphocytes (Tnaïve) and terminally differentiated effector cells (Temra) using flow cytometry technique. The proliferative activity of Tcm, Tem and Tnaïve was evaluated in response to PHA as a functional marker of T cells. We have found that the percentage of peripheral CD4+TemCD62L+ and CD8+TemCD62L+ cells in the patients with asthma exacerbation was significantly reduced, if compared to the donors. Following PHA stimulation, these differences in T cell subsets between the groups of patients and donors were not detectable. We performed a correlation analysis between the memory T cell contents and age of the subjects studied. It was shown that the relative amounts of CD4+ and CD8+ memory cells increased with age in asthmatics, but not in healthy donors. Analysis of mitogen-induced proliferation showed that Tcm and Tnaïve cells proliferated more actively than other subpopulations in both groups. Meanwhile, the proliferative activity of CD4+T lymphocytes and subsets of CD8+Tcm, CD4+Tcm and CD4+Tem62L was higher in the group of asthma patients in remission state than in the patients with exacerbating disease, and healthy donors. The revealed increase in the relative number of memory T cells with age suggests that these cells participate in development of bronchial asthma. Proliferative response of the studied subpopulations, which was comparable to the donor values, suggests a functional maintenance of memory T cells and naïve T lymphocytes in bronchial asthma. The increased proliferation of some T-cell subpopulations in asthmatics in remission suggests an activated state of memory T cells. The observed decrease in the number of CD4+TemCD62L+ and CD8+TemCD62L+ in patients with asthma exacerbation may be, by our opinion, associated with an active inflammatory process in the airways.

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Effect of memory CD4+ T cells’ signal transducer and activator of transcription (STATs) functional shift on cytokine-releasing properties in asthma

Cited by 9 publications

References 24 publications

The pathophysiological role of mitochondrial oxidative stress in lung diseases

The pathophysiological role of mitochondrial oxidative stress in lung diseases

Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis

CONTENTS OF CD4<sup>+</sup> AND CD8<sup>+</sup> EFFECTOR MEMORY CELLS AND PROLIFERATIVE ACTIVITY OF T LYMPHOCYTES IN BRONCHIAL ASTHMA

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