The effects of anti-IL17 antibody administration in asma-copd association syndrome (Acos), using a cigarette smoke exposure model

• Grant number: 20/12863-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2022
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Grantee: Alyne Riani Moreira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/02537-5 - Characterization of asthma-COPD overlap syndrome (ACOS): experimental and clinical studies, AP.TEM

Abstract

Obstructive respiratory diseases - asthma and COPD - have been widely studied, however, in recent years, a variant of these diseases, with characteristics of both, called asthma-overlap syndrome-COPD (ACO) has aroused interest in the scientific community. However, studies are lacking that offer a better understanding of the pathophysiology of the overlap of asthma and COPD and the mechanisms involved in modulating these responses. ACO predominantly affects the airways and is characterized by persistent airflow limitation due to an inflammatory process. Inflammatory responses in asthma and COPD involve both the innate and the adaptive immune response. Both in experimental models of asthma and in COPD, our group has already demonstrated the importance of the Th17 response in the development and progression of these diseases. In COPD, we have already demonstrated in a clinical and experimental study that a failure to control the inflammatory process mediated by Treg cells is present.Thus, in this study, to evaluate the role of the imbalance between the Th17 and Treg responses in an overlapping model of asthma and COPD. We will evaluate the effects of administration of an anti-IL-17 antibody on the signaling mediated by the intracellular proteins SOCS and STATs on the differentiation of TCD4 + cells in Th17 and Treg. For this C57Bl / 6 mice will be submitted to a pulmonary emphysema protocol for exposure to cigarette smoke for 30 minutes, twice a day, 5 days a week, for 2 months, after a month of exposure the Acos group will have OVA inhalations or saline, followed by treatment with or without anti-IL-17. Group control; OVA Group; Smoke Group; ACOS Group; Control-anti-IL-17 Group; OVA-anti-IL-17 group; Anti-IL-17 smoke group; ACOS-antiIL17 Group. In the end of the exposures, the animals will be anesthetized to evaluate the mechanics, the morphometric analysis of the average alveolar diameter, we will quantify the density of macrophages and neutrophils, as well as positive cells for IL-17, NFkB, TGF-², IFN-³, IL-2, IL-10.. We will evaluate the expression of IL-6 and IL-17, IL-4, IL-5, IL-13 by ELISA and gene expression for ROR gamma t and FOXP 3 by Real Time PCR.