Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 147, Issue 3, Pages 921-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2020.06.034
Keywords
Asthma; lncRNA; macrophage activation; BAZ2B
Categories
Funding
- National Key RAMP
- D Program of China [2016YFC1305102]
- National Natural Science Foundation of China [81671561, 81974248, 81900751]
- International Joint Laboratory Program of National Children's Medical Center [EK1125180109]
- Program for Outstanding Medical Academic Leader [2019LJ19]
- Shanghai Municipal Planning Commission of Science and Research Fund [201740065, 20174Y0079]
- Shanghai Pujiang Program [16PJ1401600]
- Shanghai Committee of Science and Technology [19ZR1406400, 16411950700]
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Dysregulated expression of long noncoding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) of children with asthma, especially upregulation of lnc-BAZ2B, promotes M2 macrophage activation and exacerbates lung inflammation. The interaction between lnc-BAZ2B and BAZ2B contributes to the pathogenesis of asthma and suggests a potential therapeutic and diagnostic target for children with asthma.
Background: Dysregulation of long noncoding RNAs (lncRNAs) is associated with a variety of human diseases; however, whether they have a role in childhood asthma is unknown. Objective: We sought to determine the differential expression profiles of lncRNAs in PBMCs of children with asthma and the mechanisms underlying the effects of lncRNAs on the pathogenesis of asthma. Methods: The differential expression profiles of lncRNAs were analyzed by transcriptome microarray. The effects and mechanisms by which lncRNAs influence macrophageactivation were detected by real-time quantitative PCR, Western blot, RNase protection assay, and chromatin immunoprecipitation assay. The roles played by lncRNAs in asthma were tested in a cockroach allergen extract (CRE)-induced mouse model. Results: We identified 719 lncRNAs that were differentially expressed in PBMCs of children with asthma, 502 of which were upregulated and 217 were downregulated. An lncRNA of unknown function, lnc-BAZ2B, was dominantly expressed in monocytes and significantly upregulated in children with asthma. lnc-BAZ2B promotes M2 macrophage activation by enhancing BAZ2B expression and exacerbated lung inflammation in an M2 macrophage-associated CRE-induced asthma model. Mechanistically, lnc-BAZ2B promoted the expression of its cis target gene BAZ2B by stabilizing its pre-mRNA. BAZ2B, a reader of H3K14ac modification, enhanced the transcription of IRF4 and promoted M2 macrophage activation. lnc-BAZ2B expression was correlated with that of BAZ2B in PBMCs from children with asthma. Baz2b knockdown could alleviate asthma severity in a CRE-induced asthma model. Conclusion: lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma and may serve as a potential therapeutic and diagnostic target in children with asthma.
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