The respiratory epithelium as a immune response mediator in COPD pathogenesis

• Grant number: 14/15819-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Grantee: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Mariangela Macchione ; Thais Mauad

Abstract

Although smoking is the main etiological factor of COPD, only 20% of the smoking population develops this disease, indicating that intrinsic host factors interfere in its pathogenesis. Studies suggest the importance of immune regulation in the progressive course of COPD and the importance of respiratory epithelium in the control and maintenance of this response. Aims: Develop two sub-projects: 1) An experimental model, in which we will evaluate the importance of the respiratory epithelium as a regulator of innate and adaptive immunity during the development of COPD in mice and Project 2) A comparative study between obstructive smokers (COPD) and non obstructive smokers in which we will analyze the differences in inflammatory profile (innate and adaptive immunity) in airways. Methods: For Sutdy 1 we will use C57BL / 6 mice exposed to cigarette smoke to induce COPD during 1, 3 and 6 months (Smoke Groups 1, 3 and 6 m, respectively); The control group will be exposed to ambient air (Control Groups 1, 3 and 6 m). Immunostainings will be made in lung tissue for quantification by morphometric analysis of CD4 +, CD8 + regulatory T lymphocytes and B; interleukins IL-17, IL-10, IL-13; INF-³, NF-kB, GM-CSF, TSLP, Granzyme-B, galectin-3 and MUC5AC. For Project 2, We will analyze samples from lung tissue of individuals who underwent pulmonary resection for metastatic tumor, divided into three groups: Control (nonsmokers), Obstructive Smokers and Non Obstructive Smokers. Immunohistochemistry and morphometric analysis will be performed to quantify the CD4 + and CD8 +, TGF-² regulatory T cells and B cells, the expression of chemokines such as IL-10, IL-17, CCL19 and BAFF in airways and lymphoid tissue cells associated with the bronchi (Balts) of these individuals. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ITO, JULIANA TIYAKI; DE BRITO CERVILHA, DANIELA APARECIDA; LOURENCO, JULIANA DIAS; GONCALVES, NATALIA GOMES; VOLPINI, RILDO APARECIDO; CALDINI, ELIA GARCIA; LANDMAN, GILLES; LIN, CHIN JIA; PEREIRA VELOSA, ANA PAULA; ROSOLIA TEODORO, WALCY PAGANELLI; et al. Th17/Treg imbalance in COPD progression: A temporal analysis using a CS-induced model. PLoS One, v. 14, n. 1, JAN 10 2019. (14/15819-8)

SALES, DAVI S.; ITO, JULIANA T.; ZANCHETTA, IVY A.; ANNONI, RAQUEL; AUN, MARCELO V.; FERRAZ, LUIZ FERNANDO S.; CERVILHA, DANIELA A. B.; NEGRI, ELNARA; MAUAD, THAIS; MARTINS, MILTON A.; et al. Regulatory T-Cell Distribution within Lung Compartments in COPD. COPD-Journal of Chronic Obstructive Pulmonary Disease, v. 14, n. 5, p. 533-542, 2017. (14/15819-8)