Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF-β and IL-8 production by A549 cells

Abstract

Summary Secretory IgA (SIgA) is a well‐known mucosal‐surface molecule in first‐line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non‐IPF subjects. An in‐vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)‐β and interleukin (IL)‐8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA‐induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF‐β and IL‐8.

SIgA in various pulmonary diseases

“…Some studies have shown that SIgA can bind to the surface of A549 cells. A549 is usually used as a cell line with AT2 cell phenotype in vitro experiments, which can promote the production of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)‐β [ 83 ]. Notably, these cytokines are involved in the pathogenesis of IPF [ 84 – 86 ].…”

More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

“…Equipped with less receptors but still responsive to IgA are neutrophils, dendritic cells, macrophages, basophils and even epithelial lining cells that express the transferrin receptor such as alveolar-type 2 cells (170). An additional, so far unidentified receptor is present on M cells (microfold cells) (171,172).…”

Exhaled Biomarkers in Idiopathic Pulmonary Fibrosis—A Six-Month Follow-up Study in Patients Treated with Pirfenidone

“…The comparison of the EBC cytokine concentrations between nontreated patients with IPF and controls showed a significantly higher EBC concentration of IL-8 in the latter. This is a rather unexpected finding, as it is not in line with earlier observations that almost uniformly support the involvement of IL-8 as a promoter of fibrogenesis [28][29][30]. Elevated serum concentrations of IL-8 were found in patients with IPF compared to controls by Ziora et al [4].…”