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Association between particulate matter containing EPFRs and neutrophilic asthma through AhR and Th17
- Source :
- Respiratory Research, Vol 22, Iss 1, Pp 1-16 (2021), Respiratory Research
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background Epidemiological data associate high levels of combustion-derived particulate matter (PM) with deleterious respiratory outcomes, but the mechanism underlying those outcomes remains elusive. It has been acknowledged by the World Health Organization that PM exposure contributes to more than 4.2 million all-cause mortalities worldwide each year. Current literature demonstrates that PM exacerbates respiratory diseases, impairs lung function, results in chronic respiratory illnesses, and is associated with increased mortality. The proposed mechanisms revolve around oxidative stress and inflammation promoting pulmonary physiological remodeling. However, our previous data found that PM is capable of inducing T helper cell 17 (Th17) immune responses via aryl hydrocarbon receptor (Ahr) activation, which was associated with neutrophilic invasion characteristic of steroid insensitive asthma. Methods In the present study, we utilized a combination of microarray and single cell RNA sequencing data to analyze the immunological landscape in mouse lungs following acute exposure to combustion derived particulate matter. Results We present data that suggest epithelial cells produce specific cytokines in the aryl hydrocarbon receptor (Ahr) pathway that inform dendritic cells to initiate the production of pathogenic T helper (eTh17) cells. Using single-cell RNA sequencing analysis, we observed that upon exposure epithelial cells acquire a transcriptomic profile indicative of increased Il-17 signaling, Ahr activation, Egfr signaling, and T cell receptor and co-stimulatory signaling pathways. Epithelial cells further showed, Ahr activation is brought on by Ahr/ARNT nuclear translocation and activation of tyrosine kinase c-src, Egfr, and subsequently Erk1/2 pathways. Conclusions Collectively, our data corroborates that PM initiates an eTh17 specific inflammatory response causing neutrophilic asthma through pathways in epithelial, dendritic, and T cells that promote eTh17 differentiation during initial PM exposure.
- Subjects :
- Male
Aryl hydrocarbon receptor nuclear translocator
Neutrophils
Inflammation
Transcriptome
Combustion derived particulate matter
Diseases of the respiratory system
Immune system
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
RNA-Seq
Lung
Aryl hydrocarbon receptor
biology
RC705-779
Research
Gene Expression Profiling
ScRNA sequencing
Epithelial Cells
T helper cell
Dendritic Cells
EPFRs
Asthma
Mice, Inbred C57BL
medicine.anatomical_structure
Neutrophil Infiltration
Receptors, Aryl Hydrocarbon
Immunology
biology.protein
Cytokines
Th17 Cells
Female
Particulate Matter
Th17
medicine.symptom
Signal transduction
Single-Cell Analysis
Tyrosine kinase
Signal Transduction
Subjects
Details
- Language :
- English
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Respiratory Research
- Accession number :
- edsair.doi.dedup.....a1a20f933207eee7deded368380002ae