Transcriptomic analysis reveals diverse gene expression changes in airway macrophages during experimental allergic airway disease

Wellcome Open Research

article

William J. Branchett¹  Anne O'Garra¹  Clare M. Lloyd¹ 

[1] National Heart and Lung Institute, Imperial College London;Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London;Laboratory of Immunoregulation and Infection, The Francis Crick Institute

关键词: Macrophage;    lung;    airway;    allergy;    asthma;    transcriptomics;    house dust mite;    mouse models;   

DOI  :  10.12688/wellcomeopenres.15875.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Airway macrophages (AMs) are the most abundant leukocytes in the healthy airway lumen and have a highly specialised but plastic phenotype that is governed by signals in the local microenvironment. AMs are thought to maintain immunological homeostasis in the steady state, but have also been implicated in the pathogenesis of allergic airway disease (AAD). In this study, we aimed to better understand these potentially contrasting AM functions using transcriptomic analysis.Methods: Bulk RNA sequencing was performed on AMs (CD11c+ Siglec F+ CD64+ CD45+ SSChi) flow cytometry sorted from C57BL/6 mice during experimental AAD driven by repeated house dust mite inhalation (AMsHDM), compared to control AMs from non-allergic mice. Differentially expressed genes were further analysed by hierarchical clustering and biological pathway analysis.Results: AMsHDM showed increased expression of genes associated with antigen presentation, inflammatory cell recruitment and tissue repair, including several chemokine and matrix metalloproteinase genes. This was accompanied by increased expression of mitochondrial electron transport chain subunit genes and the retinoic acid biosynthetic enzyme geneRaldh2. Conversely, AMsHDM displayed decreased expression of a number of cell cycle genes, genes related to cytoskeletal functions and a subset of genes implicated in antimicrobial innate immunity, such asTlr5,Il18 andTnf. Differential gene expression in AMsHDM was consistent with upstream effects of the cytokines IL-4 and IFN-γ, both of which were present at increased concentrations in lung tissue after HDM treatment.Conclusions: These data highlight diverse gene expression changes in the total AM population in a clinically relevant mouse model of AAD, collectively suggestive of contributions to inflammation and tissue repair/remodelling, but with decreases in certain steady state cellular and immunological functions.

【 授权许可】

CC BY