Epithelial pIgR: A new player in idiopathic pulmonary fibrosis?

Introduction: Epithelial dysfunction, including bronchiolization and type 2 alveolar cells (AEC2) hyperplasia, is a hallmark of idiopathic pulmonary fibrosis (IPF). A recent study linked IgA level to IPF prognosis. Therefore, we investigated the involvement of the polymeric immunoglobulin receptor (pIgR), the IgA transporter across epithelium, in IPF. Methods: Surgical lung samples from IPF patients and control subjects were immunostained for pIgR and pro-SPC (AEC2). In vivo experiments were performed in a recent model of chronic fibrosis that closely recapitulates IPF: 12 weeks-old C57/B6 pIgR-/- mice, as compared to littermate controls (WT), were treated with 6 successive instillations of 0.015 IU of bleomycin (BLM) or control NaCl every 12 days (d1-60). Broncho-alveolar lavage was harvested for cell counting and lung sections were stained by HE, Sirius Red and Masson’s trichrome at day 95. Lung fibrosis was quantitatively assessed by the modified Ashcroft score and OH-proline assay (µg/lobe). Results: Immunostaining of human IPF lungs revealed an ectopic expression of pIgR in IPF but not in control lungs, within AEC2 clusters. These findings were confirmed in lungs from BLM-treated mice. In addition, pIgR-/- mice displayed significantly less fibrosis as compared to control mice (96.27±30.55 vs 133.70±19.46, mean ± SD OH-proline µg/lobe, p=0.01), which correlated with histologic findings. There was no significant difference regarding inflammatory cell counts in BAL. Discussion Our preliminary data indicate an involvement of the pIgR axis in lung fibrosis, supporting the role of aberrant pIgR expression in IPF pathogenesis. Next steps will include studies of a cohort of IPF patients and of the underlying mechanisms