Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses
Juliana Dias Lourenço, Walcy Rosólia Teodoro, Denise Frediani Barbeiro, Ana Paula Pereira Velosa, Larissa E. F. Silva, Júlia Benini Kohler, Alyne Riani Moreira, Marcelo Vívolo Aun, Isadora C. da Silva, Frederico Leon Arrabal Fernandes, Elnara Márcia Negri, Jefferson Luiz Gross, Iolanda de Fátima Lopes Calvo Tibério, Juliana Tiyaki Ito, Fernanda Degobbi Tenório Quirino dos Santos Lopes
Abstract
Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, RORγt, Foxp3, interleukin (IL)-6, -17, -10, and TGF-β was assessed by RT-qPCR. IL-6, -17, -10, and TGF-β levels were determined by ELISA. We observed increased STAT3, RORγt, Foxp3, IL-6, and TGF-β gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, RORγt, IL-6, and TGF-β gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.