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Clin Exp Immunol ; 199(3): 326-336, 2020 03.
Article in English | MEDLINE | ID: mdl-31660581

ABSTRACT

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)-ß 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-ß and IL-8.


Subject(s)
Idiopathic Pulmonary Fibrosis/immunology , Immunoglobulin A, Secretory/immunology , Interleukin-8/immunology , Lung/immunology , Transforming Growth Factor beta/immunology , Vascular Endothelial Growth Factor A/immunology , A549 Cells , Aged , Aged, 80 and over , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, CD/metabolism , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/immunology , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Immunoglobulin A, Secretory/metabolism , Immunoglobulin A, Secretory/pharmacology , Interleukin-8/genetics , Interleukin-8/metabolism , Lung/drug effects , Lung/metabolism , Male , Middle Aged , RNA Interference , Receptors, Transferrin/genetics , Receptors, Transferrin/immunology , Receptors, Transferrin/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
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