Role of CCR7 on dendritic cell-mediated immune tolerance in the airways of allergy-induced asthmatic rats

摘要

Dendritic cells (DCs) have an important role in initiating and maintaining the immune inflammatory response in allergic asthma, and CC chemokine receptor 7 (CCR7) is directly involved in the pathogenesis of DC- and T cell-mediated allergic asthma. The present study aimed to investigate the effects of CCR7 on DC-mediated immune tolerance in allergic asthma. In the present study, bone marrow-derived DCs were transfected with an adenovirus encoding the rat CCR7 gene or a short hairpin RNA targeting CCR7 (sh-CCR7). Rats injected with DCs overexpressing CCR7 or presenting CCR7 knockdown were examined. After the rats were injected with DCs via the tail vein, bronchoalveolar lavage fluid was collected to assess its cellular composition. The protein expression levels of CCR7 in DCs were determined using immunohistochemistry and western blot analysis. The protein expression levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-10, IL-12, transforming growth factor-β (TGF-β) and immunoglobulin E (IgE) were determined by ELISA. Compared with the control group, the protein expression level of CCR7 was significantly higher in the CCR7 overexpression group and significantly lower in sh-CCR7 group. Similarly, the number of DCs was higher in the CCR7 overexpression group and lower in the sh-CCR7 group. The protein expression levels of IL-10 and TGF-β were significantly lower in the CCR7 overexpression group and higher in the sh-CCR7 group. In addition, the expression levels of IL-4, IL-12, IFN-γ and IgE were higher in the CCR7 overexpression group and lower in the sh-CCR7 group. The present results suggested that the role of cytokines and IgE in immune inflammation and immune tolerance in allergic asthma may be associated with the expression level of CCR7 in DCs, suggesting that CCR7 may serve a role in DC-mediated immune tolerance in allergic asthma.