Asthma Induction by Dendritic Cells and Th2 Cells
树突状细胞和 Th2 细胞诱导哮喘
基本信息
- 批准号:6841211
- 负责人:
- 金额:$ 34.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-01-01 至 2007-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Asthma is an important disease that afflicts 5% of the general population. Atopic asthma is caused by biased-T helper 2 (Th2) responses to allergens. In a mouse model, mice primed intratracheally with Ag-pulsed dendritic cells and challenged with Ag developed airway hyperresponsiveness, and lung eosinophilia and inflammation. Lungs have a more Th2-biased environment and primed T cells seem to divide faster in the lungs than lymph nodes in Ag-challenged mice, although the lymph node is believed to be the site of T cell activation and development. In this study, lung DC have been found to be composed of multiple subset. Studies on DC migration suggest that secondary lymphoid chemokine (SLC/CCL21) may be a key chemokine for DC migration to draining LN. In the lung but not lymph nodes of lung-immunized mice, large numbers of interferon-gamma-producing CD8+ T cells (Tc1) were present, resulting in a more Th2-baised environment in the lungs. These results support the hypothesis that: "a DC subset that presents antigen in lungs and mediates a Th2-biased response occurs in lungs. For T lymphocyte and DC migration to lymph nodes, SLC is a major mediator. Because Th1 and Tc1 cell numbers are very low in the inflammatory lungs, activated T cells readily develop into Th2 cells." In this proposal, experiments are designed to support this hypothesis. The aims consist of: (1) the isolation and functional studies of DC subsets in lungs; (2) the studies of CCR7/SLC interaction as a key chemokine receptor/chemokine interaction for lung DC and T cell migration to lymph nodes. The roles of other important candidate chemokine receptors such as CCR2 in mediating DC migration will also be examined; and (3) the studies of the migration of IFN-gamma-producing CD8+ T cells away from lungs during asthma pathogenesis. These studies will clarify the roles of DC and CD8+ T cells in the biased-Th2 lung response in asthma and provide a novel mechanism for Th2-biased responses during asthma pathogenesis. The results may provide additional therapeutic strategies in asthma by the interference of SLC functions and by regulating the migration of DC, Th1, and IFN-gamma-producing CD8+ T cells.
描述(由申请人提供):哮喘是一种重要的疾病,困扰着5%的普通人群。 特应性哮喘是由偏性辅助性T细胞2(Th 2)对过敏原的反应引起的。 在小鼠模型中,用银脉冲树突状细胞内致敏并用银激发的小鼠出现气道高反应性、肺嗜酸性粒细胞增多和炎症。 肺具有更偏向Th 2的环境,并且在Ag激发的小鼠中,致敏的T细胞似乎在肺中比淋巴结分裂得更快,尽管淋巴结被认为是T细胞活化和发育的部位。 在这项研究中,发现肺DC由多个亚群组成。 对DC迁移的研究表明,次级淋巴细胞趋化因子(SLC/CCL 21)可能是DC向引流LN迁移的关键趋化因子。 在肺免疫小鼠的肺而不是淋巴结中,存在大量产生干扰素-γ的CD 8 + T细胞(Tc 1),导致肺中更多的Th 2-基础环境。 这些结果支持以下假设:“在肺中呈递抗原并介导Th 2偏向性应答的DC亚群发生在肺中。 SLC是T淋巴细胞和DC向淋巴结迁移的主要介导者。 由于Th 1和Tc 1细胞数量在炎症性肺中非常低,活化的T细胞很容易发育成Th 2细胞。“在这个提议中,实验的目的是支持这一假设。 其目标包括:(1)肺内DC亚群的分离和功能研究;(2)CCR 7/SLC相互作用作为肺DC和T细胞向淋巴结迁移的关键趋化因子受体/趋化因子相互作用的研究。 其他重要的候选趋化因子受体如CCR 2在介导DC迁移中的作用也将被检查;和(3)在哮喘发病过程中产生IFN-γ的CD 8 + T细胞从肺中迁移的研究。 这些研究将阐明DC和CD 8 + T细胞在哮喘偏性Th 2肺应答中的作用,并为哮喘发病过程中的Th 2偏性应答提供新的机制。 这些结果可能通过干预SLC功能和调节DC、Th 1和产生IFN-γ的CD 8 + T细胞的迁移,为哮喘提供额外的治疗策略。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sun-Sang Joseph Sung其他文献
Sun-Sang Joseph Sung的其他文献
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