DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation.
J Allergy Clin Immunol
; 150(5): 1178-1193.e13, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35724763
ABSTRACT
BACKGROUND:
DJ-1 is an antioxidant protein known to regulate mast cell-mediated allergic response, but its role in airway eosinophilic interactions and allergic inflammation is not known.OBJECTIVE:
The aim of this study was to investigate the role of DJ-1 in airway eosinophilic inflammation in vitro and in vivo.METHODS:
Ovalbumin-induced airway allergic inflammation was established in mice. ELISA was adopted to analyze DJ-1 and cytokine levels in mouse bronchoalveolar lavage fluid. Transcriptional profiling of mouse lung tissues was conducted by single-cell RNA-sequencing technology. The role of DJ-1 in the differentiation of airway progenitor cells into goblet cells was examined by organoid cultures, immunofluorescence staining, quantitative PCR, and cell transplantation in normal, DJ-1 knockout (KO), or conditional DJ-1 KO mice.RESULTS:
This study observed that DJ-1 was increased in the lung tissues of ovalbumin-sensitized and challenged mice. DJ-1 KO mice exhibited reduced airway eosinophil infiltration and goblet cell differentiation. Mechanistically, we discovered that eosinophil-club cell interactions are reduced in the absence of DJ-1. Organoid cultures indicated that eosinophils impair the proliferative potential of club cells. Intratracheal transplantation of DJ-1-deficient eosinophils suppresses airway goblet cell differentiation. Loss of DJ-1 inhibits the metabolism of arachidonic acid into cysteinyl leukotrienes in eosinophils while these secreted metabolites promote airway goblet cell fate in organoid cultures and in vivo.CONCLUSIONS:
DJ-1-mediated interactions between airway epithelial progenitor cells and immune cells are essential in controlling airway goblet cell metaplasia and eosinophilia. Blockade of the DJ-1 pathway is protective against airway allergic inflammation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Eosinofilia
/
Eosinófilos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article