國家衛生研究院 NHRI:Item 3990099045/12254

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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:	[Shau-Ku Huang] Periodical Articles

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