Amphiregulin-expressing CD8 T cells are associated with asthma severity 3423

Abstract Description Severe asthma is characterized by persistent inflammation of the bronchial (airway) tissue that is poorly responsive to corticosteroid treatment. Because of the difficulties in obtaining sufficient quantity of bronchial tissue samples from severe asthmatics, unbiased studies that examine the phenotype, clonality and antigen-specificities of T cells present at the site of inflammation are lacking. Here, we performed the single-cell transcriptomic and T cell receptor (TCR) analysis of cells directly isolated from bronchial tissue samples of patients with severe (n = 13) and mild asthma (n = 12). The vast majority of immune cells present in the bronchial tissue were T cells. Single-cell TCR analysis showed that a large fraction of both CD8+ and CD4+ T cells were clonally-expanded, implying potential antigen recognition and expansion in the bronchial tissue of asthmatics. Surprisingly, the degree of clonal expansion and proportion of CD8+ T cells was greater when compared to CD4+ T cells, the canonical T cell type implicated in asthma pathogenesis. CD8+ T cells in the bronchial tissue displayed features of tissue-resident memory T (TRM) cells, expressing both CD103 and CD69. Notably, CD8+ TRM cells isolated from severe asthmatics expressed significantly increased levels of transcripts encoding for molecules linked to cytotoxicity (GZMB), pro-inflammatory cytokines (CCL4) and pro-fibrotic molecules (AREG), suggesting that they may play a pathogenic role in severe asthma. Funding Sources Supported by NIAID U19 AI070535; NIH R01 HL114093-09; Bowes Foundation; and BioLegend. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)