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. 2020 Jan 21:2020:1387952.
doi: 10.1155/2020/1387952. eCollection 2020.

Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4+ T Cells into Th17 Cells

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Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4+ T Cells into Th17 Cells

Jifeng Liu et al. J Immunol Res. .

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.

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Conflict of interest statement

All authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of CSE and EM on the expression of costimulatory molecules (CD40 and CD86) in DCs. (a, c) Effects of CSE and EM on CD40 expression (n = 6). (b, d) Effects of CSE and EM on CD86 expression (n = 6). (The height of the bar chart represents the mean and the height of the error line indicates the standard errors of the means in the histograms.)
Figure 2
Figure 2
Effects of CSE and EM on DCs polarizing CD4+ T cells into Th17 cells. Numbers of Th17 cells in the various groups are shown (n = 6). (The height of the bar chart represents the mean and the height of the error line indicates the standard errors of the means in the histogram).
Figure 3
Figure 3
Effects of CSE and EM on the DC-induced expression of RORγt mRNA in the MLR. RORγt mRNA levels were evaluated by quantitative RT-PCR (n = 6). (The height of the bar chart represents the mean and the height of the error line indicates the standard errors of the means in the histogram.)
Figure 4
Figure 4
Effects of EM on the secretion of IL-17A and IL-17F in the CSE-exposed DC/MLR group. The levels of IL-17A and IL-17F were evaluated using Quantibody array kits (n = 6). (The height of the bar chart represents the mean and the height of the error line indicates the standard errors of the means in the histograms).

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