研究显示小剂量5-氟尿嘧啶（5-FU,50mg/kg）具有免疫调节效应，可以选择性诱导炎症环境下炎性树突状细胞数量减少。目前认为肺炎性树突状细胞参与哮喘Th2反应，而课题组初步发现小剂量5-FU可以抑制哮喘小鼠气道炎症。因此，假设小剂量5-FU通过诱导肺炎性树突状细胞数量减少抑制哮喘Th2反应。为此，以野生型BALB/c、CCR2-/-和CD11c-DTR转基因C57BL/6、人源化NOD/SCID小鼠建立哮喘模型，观察：（1）小剂量5-FU对不同小鼠哮喘模型Th2反应、肺和纵隔淋巴结炎性树突状细胞数量及纵隔淋巴结树突状细胞表型和功能的影响；（2）过继转移炎性树突状细胞对小剂量5-FU介导的哮喘小鼠Th2反应抑制作用的影响；（3）小剂量5-FU是否诱导哮喘小鼠肺炎性树突状细胞凋亡导致其数量减少。探讨小剂量5-FU是否通过诱导肺炎性树突状细胞凋亡导致其数量减少进一步抑制哮喘Th2反应。

5-Fluorouracil (5-FU), a pyrimidine analog with antimetabolite activity, is one of the chemotherapeutic drugs widely used for the treatment of several cancers in optimal doses. It has now become clear that this drug exhibits several immunomodulatory effects. Previous study has suggested that 5-FU, at low and noncytotoxic concentration (50 mg/kg), can induce the reduction of inflammatory dendritic cells at the inflammatory sites and prevent their accumulation in the draining lymph nodes. Many reports have found that lung inflammatory dendritic cells can induce the differentiation of Th2 cells, and thereby drive Th2 cell-mediated immune responses in asthma. In our preliminary study, our data showed that low-dose 5-FU could suppress airway inflammation in an ovalbumin (OVA)-induced mouse model of allergic asthma. As such, it is hypothesized that low-dose 5-fluorouracil may suppress Th2 responses through the induction of the reduction of lung inflammatory denfritic cells in asthma. For this purpose, wild-type BALB/c mice, CCR2-/--C57BL/6 mice, CD11c-DTR (diphtheria toxin receptor, DTR) transgenic C57BL/6 mice, and humanized non-obese diabelic (NOD)/severe combined immunodeficiency (SCID) mice were used to establish asthmatic model and investigate: (1) the effects of low-dose 5-FU on Th2 responses, the number of inflammatory dendritic cells in the lung and mediastinal lymph node, and the phenotype and function of dendritic cells in mediastinal lymph node in an OVA-induced different mouse model of asthma; (2) the effects of adopive transfer of inflammatory dendritic cells on the inhibitory roles of low-dose 5-FU in Th2 responses in an OVA-induced mouse model of asthma; (3) the effect of low-dose 5-FU on the apoptosis of lung inflammatory dendritic cells in an OVA-induced mouse model of asthma. The aim of this study is to investigate that low-dose 5-FU may suppress Th2 responses through the reduction of lung inflammatory dendritic cells mediated by the apoptosis of these cells in asthma.