Loading...
|
Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/12254
|
| Title: | PM2.5 disturbs the balance of Th17/Treg cells by targeting Got1 and HIF-1alpha in an asthma model |
| Other Titles: | PM2.5 disturbs the balance of Th17/Treg cells by targeting Got1 and HIF-1α in an asthma model |
| Authors: | Sun, L;Fu, J;Lin, SH;Sun, JL;Xia, L;Lin, CH;Liu, L;Zhang, C;Yang, L;Xue, P;Wang, X;Huang, S;Han, X;Chen, HL;Huang, MS;Zhang, X;Huang, SK;Zhou, Y |
| Contributors: | National Institute of Environmental Health Sciences |
| Abstract: | BACKGROUND: Epidemiologic evidence suggests that exposure to particulate matter </=2.5 mum (PM2.5) aggravates asthma. OBJECTIVE: Investigate the underlying mechanisms between PM2.5 exposure and asthma severity. METHODS: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4(+) T cell-specific aryl hydrocarbon receptor (AhR) null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of T-helper 17/T-regulatory (Th17/Treg) cells were investigated by flow cytometry and quantitative reverse-transcription polymerase chain reaction. Mechanisms were investigated by mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing and glycolysis rates. RESULTS: PM2.5 impaired differentiation of Treg cells, promoted differentiation of Th17 cells, and aggravated asthma in an AhR-dependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of Th17 cells by up-regulating hypoxia-inducible factor-1alpha expression and enhancing glycolysis via AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase (Got)1 expression via AhRs and accumulation of R-2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase-2 activity, resulting in hypermethylation in the forkhead box p3 locus and impaired differentiation of Treg cells. A Got1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of Th17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on Th17/Treg imbalance were noted in human T cells and, in a case-control design, PAH exposure appeared to be a potential risk factor for asthma. CONCLUSIONS: The molecular pathways AhR-HIF-1alpha and AhR-Got1 mediate pulmonary responses upon exposure to PM2.5 through their ability to disturb the balance of Th17/Treg cells. |
| Date: | 2020-01 |
| Relation: | Journal of Allergy and Clinical Immunology. 2020 Jan;145(1):402-414. |
| Link to: | http://dx.doi.org/10.1016/j.jaci.2019.10.008 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0091-6749&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000505590800043 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85074915816 |
| Appears in Collections: | [黃嘯谷] 期刊論文
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| PUB31647966.pdf | | 6620Kb | Adobe PDF | 256 | View/Open |
|
All items in NHRI are protected by copyright, with all rights reserved.
|
