Temporal Analysis of the Intracellular Signaling Pathways Involved in Th17/Treg Response in COPD Development

Rationale: The Signal Transducer and Activator of Transcription (STAT) and Suppressor of Cytokine Signaling (SOCS) are a family of proteins that mediate the differentiation of immunological responses and are involved in COPD development. Aims: To perform a temporal analysis evaluating the role of SOCS and STAT proteins in Th17/Treg differentiation in a cigarette smoke (CS)-induced model of COPD. Methods: Mice were exposed to CS (CS group) for 30 minutes, 2 times a day, 5 days a week or to filtered air (Control group) during 3 and 6 months to analyze the expression of interleukins (IL)-17, -6, -10 and Transforming Growth Factor-β (TGF-β) by ELISA. Using immunohistochemistry, we quantified the density of positive cells for IL-17, Forkhead box P3 (FOXP3), SOCS1 and SOCS3 as well as total and phosphorylated STAT3 and 5 in peribronchovascular areas. Results: We observed a reduction of FOXP3+ and P-STAT5+ cells only in the third month. Although, we observed a decrease in the density of STAT5+ cells, IL-10 and TGF-β expression since the third month, that were remained until the end of protocol in CS group compared with Control group. On the other hand, the increase of IL-6 and IL-17 expression as well as the STAT3+, P-STAT3+ and IL-17+ cells were observed only in the sixth month. In both time points we demonstrated a reduction of SOCS3+ cells and an increase of SOCS1+ cells in CS group. Conclusion: Our data revealed a reduction in intracellular signaling for Treg differentiation previously to an increase in Th17 response in COPD development in a CS-induced model. Suppoted by FAPESP (2016/17817-8) and CAPES (1729747)