Dysfunctional Epithelial Barrier Is Characterized by Reduced <scp>E‐Cadherin</scp> in Idiopathic Subglottic Stenosis

Berges, Alexandra J.; Ospino, Rafael; Mafla, Laura M; Collins, Samuel; Chan-Li, Y.; Ghosh, Baishakhi; Sidhaye, Venkataramana K.; Lina, Ioan; Hillel, Alexander T.

doi:10.1002/lary.30951

Cited by 3 publications

References 40 publications

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A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis

So,

Collins,

Chan‐Li

et al. 2024

Otolaryngol.--head neck surg.

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ObjectiveTo present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS).Study DesignControlled ex vivo cohort study.SettingTertiary care academic hospital in a metropolitan area.MethodsFlow cytometry and single‐cell RNA sequencing were performed on 9 paired normal and scar tissue samples from iSGS patients. Flow cytometry was used to assess the presence of myeloid (CD11b, CD14, CD15, Siglec8), lymphoid (CD3, CD4, CD8, gamma delta [γδ], FOXP3), endothelial (CD31), fibroblast (CD90, SMA), and epithelial (CD326, CK5) markers.ResultsOn flow cytometry, iSGS scar is characterized by an increased presence of myeloid, lymphoid, endothelial, and fibroblast cell types, but a decreased presence of epithelial cells. In the myeloid lineage, iSGS scar samples demonstrated increased CD11b+ monocytes (P < .001), Siglec8+ eosinophils (P = .03), and CD14+ monocytes (P = .02). In the lymphoid lineage, iSGS scar demonstrated increased CD3+ T‐cells (P < .001), CD4+ helper T‐cells (P < .001), γδ+ T‐cells (P < .001), and FOXP3+ regulatory T‐cells (P = .002). iSGS scar exhibited specific increases in CD90+ (P = .04) and SMA+ (P < .001) fibroblasts but decreased CD326+ (E‐cadherin) epithelial cells (P = .01) relative to normal samples.ConclusionWe present a comprehensive flow cytometry panel for iSGS. This flow panel may serve as a common platform among airway scientists to elucidate the cellular mechanisms underpinning iSGS and other upper airway pathologies. Scar iSGS samples demonstrate a distinct cellular profile relative to normal iSGS specimens, exhibiting increased fibroblast, endothelial, and inflammatory cell types but decreased epithelium.

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A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis

So,

Collins,

Chan‐Li

et al. 2024

Otolaryngol.--head neck surg.

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Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

Direder,

Laggner,

Copic

et al. 2024

Preprint

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1AbstractIdiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

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Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

Direder,

Laggner,

Copic

et al. 2024

Front. Cell Dev. Biol.

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Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

show abstract

Dysfunctional Epithelial Barrier Is Characterized by Reduced E‐Cadherin in Idiopathic Subglottic Stenosis

Cited by 3 publications

References 40 publications

A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis

A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis

Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

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