Th17/Treg imbalance in COPD development: suppressors of cytokine signaling and signal transducers and activators of transcription proteins

Author(s):Show less -

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. ; Tiberio, Iolanda Fatima L. C. ; Ito, Juliana T. ; Lopes, Fernanda D. T. Q. S.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1, p. 11-pg., 2020-09-17.

Abstract

Th17/Treg imbalance contributes to chronic obstructive pulmonary disease (COPD) development and progression. However, intracellular signaling by suppressor of cytokine signaling (SOCS) 1 and SOCS3 and the proteins signal transducer and activator of transcription (STAT) 3 and STAT5 that orchestrate these imbalances are currently poorly understood. Thus, these proteins were investigated in C57BL/6 mice after exposure to cigarette smoke (CS) for 3 and 6 months. The expression of interleukin was measured by ELISA and the density of positive cells in peribronchovascular areas was quantified by immunohistochemistry. We showed that exposure to CS in the 3rd month first induced decreases in the numbers of STAT5+ and pSTAT5+ cells and the expression levels of TGF-beta and IL-10. The increases in the numbers of STAT3+ and pSTAT3+ cells and IL-17 expression occurred later (6th month). These findings corroborate the increases in the number of SOCS1+ cells in both the 3rd and 6th months, with concomitant decreases in SOCS3+ cells at the same time points. Our results demonstrated that beginning with the initiation of COPD development, there was a downregulation of the anti-inflammatory response mediated by SOCS and STAT proteins. These results highlight the importance of intracellular signaling in Th17/Treg imbalance and the identification of possible targets for future therapeutic approaches. (AU)

• FAPESP's process: 16/17817-8 - 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
• Grantee: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Support Opportunities: Regular Research Grants