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lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma through stabilizing BAZ2B

Li Xia1, Xiang Wang1, Lijuan Liu2

  • 1Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

The Journal of Allergy and Clinical Immunology
|July 27, 2020
PubMed

Insights

Long noncoding RNA (lncRNA) lnc-BAZ2B is upregulated in childhood asthma, promoting M2 macrophage activation and lung inflammation. This lncRNA may offer a new diagnostic and therapeutic target for pediatric asthma.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Dysregulation of long noncoding RNAs (lncRNAs) is implicated in various human diseases.
  • The role of lncRNAs in the pathogenesis of childhood asthma remains largely unexplored.

Purpose of the Study:

  • To investigate the differential expression of lncRNAs in children with asthma.
  • To elucidate the mechanisms by which lncRNAs contribute to asthma development and progression.

Main Methods:

  • Transcriptome microarray analysis identified differentially expressed lncRNAs in peripheral blood mononuclear cells (PBMCs) from asthmatic children.
  • Real-time quantitative PCR, Western blot, RNase protection assay, and chromatin immunoprecipitation assays were used to explore molecular mechanisms.
  • A cockroach allergen extract (CRE)-induced mouse model was employed to assess the functional role of lncRNAs in asthma.

Main Results:

  • 719 lncRNAs were differentially expressed in PBMCs of children with asthma, with 502 upregulated and 217 downregulated.
  • lnc-BAZ2B, a novel lncRNA, was significantly upregulated in monocytes of asthmatic children and promoted M2 macrophage activation.
  • lnc-BAZ2B enhanced BAZ2B expression by stabilizing its pre-mRNA, leading to increased IRF4 transcription and M2 macrophage activation, thereby exacerbating lung inflammation in a mouse model.

Conclusions:

  • lnc-BAZ2B plays a crucial role in promoting M2 macrophage activation and inflammation in childhood asthma.
  • lnc-BAZ2B represents a potential therapeutic and diagnostic biomarker for pediatric asthma.
Abstract

Keywords:
AsthmaBAZ2BlncRNAmacrophage activation

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