Rôle de l'interaction IgA-CD89 dans la pathogenèse de la fibrose pulmonaire

Details

Supervisors

Froidure, Antoine

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

enIdiopathic pulmonary fibrosis (IPF) is a chronic, lethal respiratory disease involving a tissue remodeling of the parenchyma, characterized by fibroblasts and extracellular matrix. Although it is mainly considered pauci-immune, recent research has shown an implication of mucosal immunity, particularly of the synthesis of immunoglobulin A (IgA). IgA appears to play a main role in IPF pathophysiology. This master’s thesis aims to study the interaction between IgA and macrophage through the CD89 receptor in the IPF. Previous experiments in this laboratory have shown that, in vitro, IgA and macrophages interact through CD89, leading to TGF-β secretion. TGF-β is a cytokine known to have a profibrotic effect. To investigate this mechanism in vivo, four strains of mice were used. These strains differ according to two criteria: whether the CD89 transgene, absent in the mice genome, was inserted and the knockout of the IgA gene. The mice received 6 doses of bleomycin intratracheally to induce a long-term pulmonary fibrosis. The intensity of the induced fibrosis, the activation of pathological mechanisms and the distribution of macrophages and B cells as well as that of IgA and B cell activating factor (BAFF) was compared between strains. Our initial hypothesis being that the CD89 strain will show a more intense fibrosis due to a secretion of TGF-β following the IgA-CD89 interaction. Our model did not demonstrate an effect of this interaction on the intensity of collagen synthesis or the TGF-β secretion. Bleomycin treated mice did not show a fibrotic state comparable to that previously observed in the laboratory or in the literature. Although the mice showed an elevation of B cells aggregates, IgA and BAFF. Those observations are also present in the IPF patient compared to healthy individuals. Through immunostaining, those aggregates showed presence of IgA, T cells and BAFF in the aggregates and macrophages were located near them. These results suggest that those aggregates are a potential center of interactions between BAFF, IgA, B and T cells and macrophages.