MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1α

Xu, Li; Sun, Wen J.; Jia, Ai J.; Qiu, Lu L.; Xiao, Bing; Lin, MingDe; Li, Jian M.; Zhang, Xiu F.; Wei, Yan; Peng, Cong; Zhang, Dong S.; Xiang, Xu

doi:10.1186/s12950-018-0191-x

Cited by 22 publications

(24 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, HIF-1α has been reported to facilitate the differentiation of Th17 cells [27], and may serve as an important signaling molecule for the induction of asthma through Th17 cells [14,15]. HIF-1α can also cause asthma by means of airway smooth muscle remodeling [28,29], which is in line with our ndings.…”

Section: Discussionsupporting

confidence: 82%

The YAP/HIF-1α/miR-182/EGR2 Axis is Implicated in Asthma Severity by Control of Th17 Cell Differentiation

Zhou

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Asthma is a heterogeneous chronic inflammatory disease of the airways, with reversible airflow limitations and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is hitherto little data about signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to ascertain whether the YAP/HIF-1α/miR-182/EGR2 axis underpins Th17 cell differentiation and asthma severity.Methods: The study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin (OVA)-induced murine asthma models, and mouse naive CD4+ T. The subpopulation of Th17 cells was examined by flow cytometry. The level of IL-17A was determined by ELISA method. ChIP-qPCR assay and dual-luciferase reporter gene assay were performed to examine interaction between HIF-1α and miR-182, miR-182 and EGR2.Results: YAP, HIF-1α, and miR-182 were found to be up-regulated but EGR2 was down-regulated in human and mouse peripheral blood mononuclear cells (PBMCs) in the context of asthma. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo findings revealed that over-expression of EGR2 undermined the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction.Conclusion: These results shed light on that the activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, providing a potential therapeutic target in asthma.

show abstract

Section: Discussionsupporting

confidence: 82%

The YAP/HIF-1α/miR-182/EGR2 Axis is Implicated in Asthma Severity by Control of Th17 Cell Differentiation

Zhou

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Other studies have illustrated that deficiency of HIF-1α can reduce eosinophil infiltration, goblet cell hyperplasia, and levels of cytokines IL-4, IL-5, and IL-13 in the lungs of OVA-induced asthma models [ 13 ], further highlighting the importance of the elevated levels of HIF-1α in asthma. Moreover, HIF-1α has been reported to facilitate the differentiation of Th17 cells [ 30 ], and may serve as an important signaling molecule for the induction of asthma by promoting Th17 cells [ 16 , 17 ]. HIF-1α can also cause asthma by means of airway smooth muscle remodeling [ 31 , 32 ], which is in line with our findings.…”

Section: Discussionmentioning

confidence: 99%

The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation

Zhou

Zhang

et al. 2021

Cell Biosci

View full text Add to dashboard Cite

Background Asthma is a heterogeneous chronic inflammatory disease of the airway, involving reversible airflow limitation and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is limited understanding of the signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to investigate if the Yes-associated protein (YAP)/hypoxia inducible factor-1α (HIF-1α)/microRNA-182 (miR-182)/early growth response 2 (EGR2) axis is involved in mediating Th17 cell differentiation and disease severity in asthma. Methods The study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin-induced murine asthma models, and mouse naive CD4+ T cells. The subpopulation of Th17 cells was examined by flow cytometry. The levels of interleukin-17A were determined by enzyme linked immunosorbent assay. Chromatin immunoprecipitation-quantitative polymerase chain reaction assays and dual-luciferase reporter gene assays were performed to examine interactions between HIF-1α and miR-182, and between miR-182 and EGR2. Results YAP, HIF-1α, and miR-182 were upregulated but EGR2 was downregulated in human and mouse peripheral blood mononuclear cells from the asthma group. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo overexpression of EGR2 countered the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction. Conclusion These results indicate that activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, thus suggesting a potential therapeutic target for asthma.

show abstract

“…CpGs cg11316510 and cg09573852 on genes RARA (retinoic acid receptor alpha) and IKBKB (Inhibitor of Nuclear Factor Kappa B Kinase), respectively, were among the IOW-ALSPAC consistent CpGs but not on the list of IOW-BAMSE consistent CpGs. Their significant involvement in lung function, as well as lung function development and pulmonary diseases such as asthma and COPD indicated the potential importance of these two CpGs and their mapped genes [11,[61][62][63][64][65][66][67][68][69][70][71]. RARA is the predominant isotype of the retinoic acid receptor (RAR) identified in alveolar type II epithelial cells and components of the retinoic acid signaling pathway [63][64][65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

Changes of DNA methylation are associated with changes in lung function during adolescence

et al. 2020

View full text Add to dashboard Cite

Background: Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosinephosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs. Methods: Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped. Results: For females, 42 CpGs showed statistically significant associations with change in FEV 1 /FVC, but none for change in FEV 1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development. Conclusions: The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

show abstract

MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1α

Cited by 22 publications

References 35 publications

The YAP/HIF-1α/miR-182/EGR2 Axis is Implicated in Asthma Severity by Control of Th17 Cell Differentiation

The YAP/HIF-1α/miR-182/EGR2 Axis is Implicated in Asthma Severity by Control of Th17 Cell Differentiation

The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation

Changes of DNA methylation are associated with changes in lung function during adolescence

Contact Info

Product

Resources

About