跨细胞
聚合免疫球蛋白受体
生物
免疫染色
蛋白酵素
分泌成分
免疫学
胰弹性蛋白酶
免疫球蛋白A
弹性蛋白酶
细胞生物学
细胞
抗体
免疫球蛋白G
免疫组织化学
酶
生物化学
内吞作用
作者
Jessica S. Blackburn,Jacob E. Schaff,Sergey Gutor,Rui-Hong Du,David E. Nichols,Taylor P. Sherrill,Austin J. Gutierrez,Matthew K. Xin,Nancy Wickersham,Yong Zhang,Michael J. Holtzman,Lorraine B. Ware,Nicholas E. Banovich,Jonathan A. Kropski,Timothy S. Blackwell,Bradley W. Richmond
标识
DOI:10.1165/rcmb.2021-0548oc
摘要
Loss of secretory IgA (SIgA) is common in chronic obstructive pulmonary disease (COPD) small airways and likely contributes to disease progression. We hypothesized that loss of SIgA results from reduced expression of pIgR (polymeric immunoglobulin receptor), a chaperone protein needed for SIgA transcytosis, in the COPD small airway epithelium. pIgR-expressing cells were defined and quantified at single-cell resolution in human airways using RNA in situ hybridization, immunostaining, and single-cell RNA sequencing. Complementary studies in mice used immunostaining, primary murine tracheal epithelial cell culture, and transgenic mice with secretory or ciliated cell-specific knockout of pIgR. SIgA degradation by human neutrophil elastase or secreted bacterial proteases from nontypeable Haemophilus influenzae was evaluated in vitro. We found that secretory cells are the predominant cell type responsible for pIgR expression in human and murine airways. Loss of SIgA in small airways was not associated with a reduction in secretory cells but rather a reduction in pIgR protein expression despite intact PIGR mRNA expression. Neutrophil elastase and nontypeable H. influenzae-secreted proteases are both capable of degrading SIgA in vitro and may also contribute to a deficient SIgA immunobarrier in COPD. Loss of the SIgA immunobarrier in small airways of patients with severe COPD is complex and likely results from both pIgR-dependent defects in IgA transcytosis and SIgA degradation.
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