The role of notch signaling pathway in CD4 + CD25 + FOXP3 + T regulatory cell balance in Chronic Obstructive Pulmonary Disease

Notch signaling is essential for airway development and progenitor/stem cell regeneration, regulation, and controlling the fate of airway epithelial cells during differentiation. This signaling pathway also regulates the Th1/Th2 and Th17/ T regulatory (Treg) cells immune balance and has a substantial influence on disease pathogenesis. The impact of the Notch signaling pathway to the pathogenesis and progression of chronic obstructive pulmonary disease (COPD) is not well understood, despite the fact that studies suggest that its dysregulation may lead to various of respiratory diseases. Our current study demonstrated the increased distribution of the Notch receptor on T regulatory cells in healthy smokers, and patients with stable, and exacerbated COPD, as compared to nonsmokers also the high level of Th1/Th2 cell ratio in exacerbated COPD patients by flow cytometry. We also studied Notch and Treg/Th17 cell balance by analyzing the expression of Foxp3, RORγt, and Notch downstream genes such as Hes5 and Hey1, in CD4+T-helper cells using RT-PCR; At the gene level, no significant differences between study groups were observed. By using the Multiplex Cytokine Assay, we measured the levels of pro- and anti-inflammatory cytokines in COPD patients and found high levels of pro-inflammatory cytokines, as well as a negative correlation between Notch expression and anti-inflammatory cytokines. Together, these data showed that the Notch signaling pathway may deteriorate the Treg cell function as well as may be one of the major drivers in COPD inflammation. Free Keywords: Notch signaling pathway, T regulatory cells, T cell imbalance, Chronic obstructive pulmonary disease, pathogenesis, inflammation, stable, exacerbated.