Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma

Area of Science:

• Pulmonary Medicine
• Immunology
• Genomics

Background:

• Asthma involves complex inflammatory pathways across various cell types and tissues.
• The transcriptomic profiles of airway epithelium and T cells in asthma remain understudied.
• Investigating cellular and tissue interactions is crucial for understanding asthma heterogeneity.

Purpose of the Study:

• To conduct a comprehensive transcriptomic assessment of airway epithelium and T cells in asthma.
• To investigate interactions between multiple cell types and tissues in asthma.
• To identify distinct molecular signatures associated with mild, moderate, and severe asthma.

Main Methods:

• Obtained epithelial brushings and flow-sorted CD3+ T cells from healthy subjects and asthma patients.
• Assessed gene expression using Affymetrix HT HG-U133+ PM GeneChips.
• Validated findings using real-time quantitative PCR.

Main Results:

• Mild asthma showed upregulated IL-13 response genes, mast cell mediators, and cystatins in the epithelium.
• Severe asthma exhibited distinct upregulated processes including neutrophilia, mucins, and oxidative stress responses.
• Sputum T cells in severe asthma displayed a significant disease signature with upregulated IL-17-inducible chemokines and neutrophil chemoattractants, indicating compartmentalized inflammation.

Conclusions:

• Activated T cells may drive neutrophilic inflammation and steroid-insensitive IL-17 responses in severe asthma.
• Innate immune pathway activation in airways suggests a key role for T cells in severe asthma.
• Transcriptomic analysis highlights tissue-specific inflammatory signatures and potential therapeutic targets in asthma.