Erythromycin Suppresses the Cigarette Smoke Extract‐Exposed Dendritic Cell‐Mediated Polarization of CD4 <sup>+</sup> T Cells into Th17 Cells
Jifeng Liu, Xiao-ning Zhong, Zhiyi He, Jianquan Zhang, Jing Bai, Guangnan Liu, Yi Liang, Leilei Ya, Xianglin Qin
Abstract
Cigarette smoke is a major effector of chronic obstructive pulmonary disease (COPD), and Th17 cells and dendritic cells (DCs) involve in the pathogenesis of COPD. Previous studies have demonstrated the anti‐inflammatory effects of macrolides. However, the effects of macrolides on the cigarette smoke extract‐ (CSE‐) induced immune response are unclear. Accordingly, in this study, we evaluated the effects of erythromycin (EM) on CSE‐exposed DCs polarizing naïve CD4 + T cells into Th17 cells. DCs were generated from bone marrow‐derived mononuclear cells isolated from male BALB/c mice and divided into five groups: control DC group, CSE‐exposed DC group, CD40‐antibody‐blocked CSE‐exposed DC group, and EM‐treated CSE‐exposed DC group. The function of polarizing CD4 + T cells into Th17 cells induced by all four groups of DCs was assayed based on the mixed lymphocyte reaction (MLR) of naïve CD4 + T cells. CD40 expression in DCs in the CSE‐exposed group increased significantly compared with that in the control group ( P < 0.05). The Th17 cells in the CSE‐exposed DC/MLR group increased significantly compared with those in the control DC/MLR group ( P < 0.05). Moreover, Th17 cells in the CD40‐blocked CSE‐exposed DC/MLR group and EM‐treated CSE‐exposed DC/MLR group were reduced compared with those in the CSE‐exposed DC/MLR group ( P < 0.05). Thus, these findings suggested that EM suppressed the CSE‐exposed DC‐mediated polarization of CD4 + T cells into Th17 cells and that this effect may be mediated through inhibition of the CD40/CD40L pathway.