Autophagy in Mononuclear Cells from Patients with Autoimmune Thyroiditis

Abstract

Autoimmune thyroiditis (AIT) is a chronic thyroid disorder wherein overstimulated CD4+T lymphocytes activate CD8+ cytotoxic T lymphocytes, thereby inducing Fas-mediated apoptosis of thyrocytes and reducing the hormonal activity of the thyroid gland. Recent studies suggest that autophagy, a process vital for maintaining cellular homeostasis through the degradation of damaged proteins and organelles in autolysosomes, is involved in the pathogenesis of autoimmune diseases. This article examines autophagy in peripheral blood mononuclear cells and the expression of key autophagy proteins (Vps34, p62, and LC3) in patients with AIT. The number of autophagosomes in the cells was tracked and assessed using flow cytometry. The expression of the protein markers was measured by western blotting. It was demonstrated that the levels of Vps34, LC3-II, and p62 increased significantly in the lymphocytes of all patients with AIT. The high level of the autophagosome protein LC3-II correlated with that of the ubiquitin-binding protein p62, which may indicate a disruption in the late stage of autophagy, i.e., in the fusion of autophagosomes with lysosomes. Impaired autophagy promotes excessive accumulation of autophagosomes in the cytoplasm, which, in turn, triggers apoptotic or necrotic cell death. Therefore, understanding the mechanisms of impaired autophagy in lymphocytes could be a promising avenue for slowing and limiting the damage associated with the onset and development of AIT.