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Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma

ABSTRACT: T cells play a central role in host protection against respiratory pathogens, but a maladaptive T cell response can lead to pulmonary diseases. Defining the biology of protective versus pathogenic T cell responses in the lungs of humans will be critical to nominate novel approaches to improve respiratory health. Previous studies have examined T cells from the lungs captured via bronchoalveolar lavage (BAL), endobronchial brushings, or biopsies. However, whether these different approaches are capturing distinct T cell phenotypes and/or clonotypes remains unclear. We aimed to evaluate and compare the transcriptional signatures of T cells isolated via BAL versus endobronchial brushings in healthy controls (HCs) and allergic asthmatics (AAs). The most significant difference in T cell subsets abundance between AAs and HCs was the enrichment of CD4 T helper type 2 (Th2) cells when comparing endobronchial brush samples (OR=26.2, P=0.002), but not when examining BAL (OR=1.7, P=0.46), indicating differences in the T cell subsets captured from the BAL versus airway mucosa specimen processing. TCR repertoire analysis revealed that brush T cells contained dramatically expanded TCR clones. Expanded T cell clones from the brush expressed high levels of resident-memory markers, suggesting the airway mucosa is enriched for TRM cells with unique TCR specificity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297584 | GEO | 2026/03/10

REPOSITORIES: GEO

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Project description:We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI. Experiment Overall Design: animals were treated by PBS, rhPBEF (IT administration), VILI (4 hours, 30 ml/kg tidal volume), or both.

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Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma

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