Idiopathic subglottic stenosis (iSGS) is a localized fibrosis of the proximal airway mucosa that occurs almost exclusively in adult, Caucasian women. Abundant T cell infiltration in subglottic scar has been demonstrated in human samples, and animal models confirm the necessity of adaptive immunity for subglottic scar formation after epithelial injury. Applying the principle that an individual’s T cell receptor (TCR) repertoire encodes their pathogen exposure history, we explored the TCR repertoire within the affected mucosa of iSGS patients. Harnessing single cell RNA sequencing (scRNAseq) of subglottic scar from 7 human samples and matched unaffected airway mucosa, we produced TCR repertoires for each patient. TCR sequences were utilized to construct repertoire structure, compare diversity, interrogate overlap, and define antigenic targets. Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH2) analysis was conducted to group T cells with common antigen targets. Results showed minimal overlap between unique patients. In each iSGS patient, the majority of highly expanded T cell clones were present in both paired scar and adjacent unaffected tissue. Network similarity analysis via GLIPH2 showed a number of T cell clusters with known viral and bacterial targets unique to subglottic scar tissue. These finding help to illustrate unique aspects of the subglottic space and may help provided insight into the pathogenesis of a rare disease of the proximal airway.
Profiling Local T Cell Receptor Repertoire in the Proximal Airway Reveals Immunologic Memory to Viral Pathogens
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Date: May 6 Presentation Time: 02:15 PM to 03:30 PM Room: Exhibit Hall F1