Secretory Cells Are the Primary Source of pIgR in Small Airways

Jessica B. Blackburn, Jacob A. Schaff, Sergey Gutor, Rui Hong Du, David Nichols, Taylor 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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)334-345
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume67
Issue number3
DOIs
StatePublished - Sep 2022

Keywords

  • airway epithelium
  • chronic obstructive pulmonary disease
  • secretory IgA
  • secretory cells

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