Effect of the Rubicon protein on LC3-associated phagocytosis by monocytes in the patients with severe atopic bronchial asthma

Atopic bronchial asthma is the most common and severe allergic disease among a wide range of similar diseases. The main pathogenesis of this disease is characterized by a disturbance of T lymphocyte homeostasis, which significantly worsens the general state of health. In atopic bronchial asthma, there is impaired process of T cell apoptosis. This entails dysregulation and maintenance of peripheral lymphocyte homeostasis. Normally, T cells must undergo apoptosis, and its products should be utilized by neighboring cells, or professional phagocytes: monocytes, macrophages, or dendritic cells. This process is altered in atopic bronchial asthma. The immune system disorders, such as autoimmunity, often result from dysregulation of lymphocyte apoptosis. This is especially true in cases of insufficient or missed clearance of apoptotic bodies.
Recently, the research and medical communities pay much attention to efferocytosis, a form of phagocytosi which proceeds by removal of apoptotic cells by phagocytes by means of LC3-associated phagocytosis (LAP). This process initiates uptake of the particles due to interactions between the phagocyte plasma membrane receptors and apoptotic cell. Further on, a single-membrane phagosome is formed in the cell with the participation of certain autophagy proteins (Beclin-1, VPS34, UVRAG, ATG5, ATG12, ATG7, ATG4, ATG4, LC3). The phagosome is enriched with LC3 protein molecules and fused with lysosomes, in which the captured “cargo” is then lysed. As a part of our work, a detailed analysis of some key protein contents at the LAP pathway was carried out for peripheral blood monocytes of patients with severe bronchial asthma. It was found that the expression of Rubicon protein is increased, thus allowing to conclude that the LAP pathway is activated in monocytes of healthy donors, thus allowing phagocytosis of dying T cells. At the same time, the components characteristic of both autophagy and LC3-associated phagocytosis are activated in the monocytes of patients with severe atopic asthma. However, one should note that decreased expression of the Rubicon protein, a putative marker of LC3-associated phagocytosis, has been clearly confirmed.

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