Impact of alveolar macrophage-mediated efferocytosis on the regulation of lung inflammation in asthma

• Grant number: 25/14067-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Luanna Victoria de Paiva Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Asthma is a chronic inflammatory disease that results in morphological and functional changes and respiratory system. Allergic asthma is triggered by a sequence of immunological events culminating in the differentiation of Th2 lymphocytes, allergen-specific IgE production by B lymphocytes, recruitment of eosinophils and activation of mast cells. Treatment for asthma includes the use of inhaled corticosteroids and bronchodilators, although 5-10% of patients are poorly responsive to this intervention.The degranulation of eosinophils and mast cells leads to apoptosis of leukocyte and structural cells, resulting in the accumulation of apoptotic cells, which must be eliminated by efferocytosis - phagocytosis and digestion of apoptotic bodies by airway macrophages. In order to discriminate the target cells, during the apoptosis process there is the externalization of phosphatidylserine, which is identified by efferocytosis receptors expressed by the phagocyte, such as the Axl receptor.Although airway macrophages constitutively express Axl, there are evidence in the literature of decreased expression of this receptor in patients with severe asthma, leading to dysfunctional efferocytosis and intensified accumulation of apoptotic cells. Thus, this project aims to investigate the impact of the inefficiency of the efferocytosis, especially Axl-dependent, on persistent airway inflammation characteristic of allergic asthma. We seek therapeutic targets that contribute to the improvement of the quality of life of asthma patients, especially those with severe asthma.