Mechanisms of artepillin C-induced myeloid derived suppressor cells in experimental allergic asthma

• Grant number: 22/16716-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Guilherme Rodrigues de Mira
• 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 associated with an exacerbation of an allergen-specific immune response that leads to tissue damage of respiratory mucosa, increase in mucus production and tissue remodeling. Asthma is characterized by the recruitment and activation of eosinophils, Th2 lymphocytes and mast cells, as well as production of allergen-specific IgE. Patients with asthma are treated with bronchodilators and corticosteroids for the control of the symptoms. However, the continuous use of corticosteroids can lead to an exogenous hypercortisolism, causing impaired metabolism and immunosuppression. Therefore, the development of adjuvant therapies is relevant on the care of patients with asthma. Previous results of our research group shows that artepillin C (ArtC), an isolated compound of the green propolis, is able to decrease the pulmonary inflammation in a mouse model of ovalbumin-induced asthma by the induction of monocytic myeloid derived suppressor cells (M-MDSC). Also, it has been reported an increase in the expression of PD-L1 (Programmed-Cell-Death-Ligand-1) on M-MDSC, which is associated to its receptor PD-1 (CD279) expressed on lymphoid cells. Besides the induction of influx of M-MDSC in the lungs, ArtC has been able to promote apoptosis in tumoral cells. However, the mechanisms involved in the reduction of the pulmonary inflammation induced by ArtC, as well by ArtC-induced M-MDSC are unknown. Therefore, we hypothesized that ArtC reduces the pulmonary inflammation in a mouse model of asthma by the induction of the PD-1/PD-1L pathway, promoting the increase of PD-L1 expression on M-MDSC. In addition, ArtC induces cell death on eosinophils, the major readout of asthma. We seek to elucidate those mechanisms to aim the use of ArtC as an adjuvant and complementary therapy on the control of the pulmonary inflammation in asthmatic individuals.