Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13

Am J Respir Crit Care Med. 2018 Jun 1;197(11):1396-1409. doi: 10.1164/rccm.201703-0561OC.


Rationale: Asthma is associated with increased lung IgE production, but whether the secretory IgA system is affected in this disease remains unknown.

Objectives: We explored mucosal IgA transport in human asthma and its potential regulation by T-helper cell type 2 inflammation.

Methods: Bronchial biopsies from asthma and control subjects were assayed for bronchial epithelial polymeric immunoglobulin receptor (pIgR) expression and correlated to T-helper cell type 2 biomarkers. Bronchial epithelium reconstituted in vitro from these subjects, on culture in air-liquid interface, was assayed for pIgR expression and regulation by IL-4/IL-13.

Measurements and main results: Downregulation of pIgR protein was observed in the bronchial epithelium from patients with asthma (P = 0.0002 vs. control subjects). This epithelial defect was not observed ex vivo in the cultured epithelium from patients with asthma. Exogenous IL-13 and IL-4 could inhibit pIgR expression and IgA transcytosis. Mechanistic experiments showed that autocrine transforming growth factor-β mediates the IL-4/IL-13 effect on the pIgR, with a partial contribution of upregulated transforming growth factor-α/epidermal growth factor receptor.

Conclusions: This study shows impaired bronchial epithelial pIgR expression in asthma, presumably affecting secretory IgA-mediated frontline defense as a result of type 2 immune activation of the transforming growth factor pathway.

Keywords: IL-13; IgA; asthma; polymeric immunoglobulin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asthma / metabolism*
  • Asthma / physiopathology*
  • Bronchi / metabolism*
  • Female
  • Humans
  • Immunoglobulin A / metabolism*
  • Immunoglobulin A, Secretory / metabolism*
  • Interleukin-4 / metabolism*
  • Male
  • Middle Aged
  • Respiratory Mucosa / metabolism*


  • Immunoglobulin A
  • Immunoglobulin A, Secretory
  • Interleukin-4