The role of SOCS and STATs proteins on the differentiation of cells CD4 + naive in the chronic obstructive pulmonary disease (COPD) development in both smokers patients and experimental model exposure to cigarette smoke

• Grant number: 16/17817-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2017
• End date: June 30, 2019
• 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: Carla Máximo Prado ; Elnara Marcia Negri ; Rodolfo de Paula Vieira

Abstract

In a previous study we demonstrated that COPD smokers showed decreased regulatory T cells density (Treg) with a decrease for their immunosuppressant interleukins TGF beta and IL-10 compared to smokers without obstruction. Also, it was also detected increased positive cells density for IL-17, featuring a Th17 response profile in these individuals. Considering the role of intracellular proteins STAT (the English "Activator of Transcription Protein") and SOCS (English "Suppressor Of Cytokine Signaling") in the differentiation of CD4 + cells naive in its subtypes Objective: We intend, in this study, to evaluate the mechanisms involved in the differentiation of CD4 + naive cells to Th17, and Treg and Th1 subtypes considering the role of STAT and SOCS proteins in COPD. We will perform assessments in tissues and plasma samples from patients and in experimental model, which will also allow us to evaluate how much the experimental model reflects the observed in humans Methods: Protocol 1: We will study patients undergoing pulmonary resection for primary metastatic tumor, divided into two groups: Non Obstructive smokers and Obstructive Smokers. Protocol 2: For the induction of pulmonary emphysema, mice will be exposed to cigarette smoke for 3 and 6 months, and the control animals remain exposed to ambient air. For both protocols, we will evaluate the interleukins -6, -10, - 17, and TGF-² and IFN-³ in lung samples and blood plasma to check systemic and local response. In the lungs we will assess the density of positive cells for IL-17 (Th17 profile), IFN-³ (Th1 profile) and Treg, STAT 3, 5 total and phosphorylated and SOCS 1 and 3. We will quantify by immunoblotting STAT 3, 5 total and phosphorylated and SOCS 1 and 3 . We will evaluate the gene expression for STAT 3, 5 and SOCS1 and 3 in tissue and plasma of individuals of the Protocol 1 by real-time PCR . (AU)

Scientific publications

(4)

(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)

DE FRANCA SILVA, LARISSA EMIDIO; LOURENCO, JULIANA DIAS; DA SILVA, KAIQUE RODRIGUES; KOHLER, JULIA BENINI; RONCON SANTANA, FERNANDA PAULA; MOREIRA, ALYNE RIANI; DE BRITO CERVILHA, DANIELA APARECIDA; SOBRAL HAMAGUCHI, SARA SUMIE; PRADO, CARLA MAXIMO; VIEIRA, RODOLFO DE PAULA; et al. Temporal analysis of the intracellular signaling pathways involved in Th17/Treg response in COPD development. European Respiratory Journal, v. 54, p. 2-pg., 2019-09-28. (16/17817-8)

LOURENCO, JULIANA D.; TEODORO, WALCY R.; BARBEIRO, DENISE F.; VELOSA, ANA PAULA P.; SILVA, LARISSA E. F.; KOHLER, JULIA B.; MOREIRA, ALYNE R.; AUN, V, MARCELO; DA SILVA, ISADORA C.; FERNANDES, FREDERICO L. A.; et al. Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses. CELLS, v. 10, n. 7, JUL 2021. (16/17817-8, 16/21408-6)

LOURENCO, JULIANA DIAS; DE FRANCA SILVA, LARISSA EMIDIO; DE GENARO, ISABELLA SANTOS; ITO, JULIANA TIYAKI; PIETROBON, ANNA JULIA; SATO, MARIA NOTOMI; GROSS, JEFFERSON LUIZ; NEGRI, ELNARA MARCIA; BARBEIRO, DENISE FREDIANI; ROSOLIA TEODORO, WALCY PAGANELLI; et al. Intracellular mechanisms of Th17/Treg differentiation in mild and moderate COPD patients. European Respiratory Journal, v. 54, p. 2-pg., 2019-09-28. (16/17817-8, 16/21408-6)

SILVA, LARISSA E. F.; LOURENCO, JULIANA D.; SILVA, KAIQUE R.; SANTANA, FERNANDA PAULA R.; KOHLER, JULIA B.; MOREIRA, ALYNE R.; VELOSA, ANA PAULA P.; PRADO, CARLA M.; VIEIRA, RODOLFO P.; AUN, MARCELO V.; et al. Th17/Treg imbalance in COPD development: suppressors of cytokine signaling and signal transducers and activators of transcription proteins. SCIENTIFIC REPORTS, v. 10, n. 1, p. 11-pg., 2020-09-17. (16/17817-8)