@article {Richmond133, author = {Bradley Richmond and Jessica Blackburn and Jacob Schaff and Sergey Gutor and David Nichols and Taylor Sherrill and Nancy Wickersham and Lorraine Ware and Michael Holtzman and Austin Gutierrez and Nicholas Banovich and Jae-Woo Lee and Timothy Blackwell}, title = {Club cells are the primary source of pIgR~in small airways}, volume = {8}, number = {suppl 8}, elocation-id = {133}, year = {2022}, doi = {10.1183/23120541.LSC-2022.133}, publisher = {European Respiratory Society}, abstract = {Background: Loss of secretory immunoglobulin A (SIgA) in small (\< 2 mm) airways is common in patients with COPD and is implicated in disease progression in animal models. However, the mechanism of SIgA loss remains unclear.Aim: Since the polymeric immunoglobulin receptor (pIgR) is required for SIgA transcytosis across the airway epithelium, we defined the cell types capable of making pIgR and investigated whether numbers of pIgR-expressing cells differ between SIgA-intact and deficient airways from COPD patients.Methods: Cell type-specific expression of pIgR was determined in human small airways by RNA in-situ hybridization, immunostaining, and single-cell RNA sequencing (scRNA-seq). Complementary in vivo studies included analyses on mice lacking pIgR specifically in ciliated or club cells (FoxJ1.Cre/Flox-pIgR and Scgb1a1.CreERT2/Flox-pIgR mice, respectively) and on primary murine tracheal epithelial cells treated with DAPT, which inhibits club cell differentiation. Percentage of pIgR-expressing cells was determined in human small airways from COPD lung explants by immunostaining.Results: Secretory cells are the dominant cell type responsible for pIgR expression in human and murine airways, although other cell types are capable of lower-level expression. Although pIgR is expressed at low levels in ciliated cells, genetic deletion of pIgR in ciliated cells did not cause emphysema typical of pIgR null mice. The percentage of pIgR-expressing cells did not differ between COPD airways with an intact and deficient SIgA immunobarrier.Discussion: pIgR is primarily expressed by club cells across multiple vertebrate species. Loss of pIgR-expressing club cells does not fully account for loss of SIgA in COPD.FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 133.This article was presented at the 2022 ERS Lung Science Conference, in session {\textquotedblleft}Poster Session 2{\textquotedblright}.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).}, URL = {https://openres.ersjournals.com/content/8/suppl_8/133}, eprint = {https://openres.ersjournals.com/content}, journal = {ERJ Open Research} }