T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production.
T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production.
复制标题
T辅助1细胞和干扰素伽马调节过敏性气道炎症和粘液产生。
DOI：
10.1084/jem.190.9.1309
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发表时间：
1999-11-01
影响因子：
15.3
通讯作者：
Bottomly, K
中科院分区：
文献类型：
--
作者：
Cohn, L;Homer, R J;Niu, N;Bottomly, K
在哮喘患者的气道中已经鉴定出CD 4辅助性T（Th）1型和Th 2细胞。Th 2细胞被认为有助于疾病的发病机制，但Th 1细胞的作用尚未明确。在小鼠模型中，我们以前报道过，转移的T细胞受体转基因Th 2细胞在呼吸道中活化，导致气道炎症，具有哮喘的许多病理特征，包括气道嗜酸性粒细胞增多和粘液产生。Th 1细胞引起的炎症与哮喘无关。在这份报告中，我们研究了Th 1细胞在调节气道炎症中的作用。当Th 1和Th 2细胞一起转移到受体小鼠中时，气道嗜酸性粒细胞增多和粘液染色显著减少。为了阐明Th 1细胞的确切作用，我们提出了以下问题：（i）Th 2诱导的应答是否受到干扰素（IFN）-γ的抑制？和（ii）在没有IFN-γ的情况下，Th 1细胞能诱导嗜酸性粒细胞增多和粘液吗？在暴露于吸入抗原的IFN-γ受体−/−受体小鼠中，Th 1细胞对气道嗜酸性粒细胞增多和粘液产生的抑制作用被消除。在缺乏IFN-γ受体信号传导的情况下，Th 1细胞诱导粘液，但不诱导嗜酸性粒细胞增多。因此，我们已经确定了粘液产生的新的调节途径;粘液可以由肺中的Th 2和非Th 2炎症反应诱导，这两者都被IFN-γ抑制。IFN-γ对嗜酸性粒细胞增多和粘液产生的阻断可能通过不同的抑制途径发生，这些抑制途径在Th 2细胞因子分泌的下游被激活，并且需要受体小鼠组织中的IFN-γ信号传导。
CD4 T helper (Th) type 1 and Th2 cells have been identified in the airways of asthmatic patients. Th2 cells are believed to contribute to pathogenesis of the disease, but the role of Th1 cells is not well defined. In a mouse model, we previously reported that transferred T cell receptor–transgenic Th2 cells activated in the respiratory tract led to airway inflammation with many of the pathologic features of asthma, including airway eosinophilia and mucus production. Th1 cells caused inflammation with none of the pathology associated with asthma. In this report, we investigate the role of Th1 cells in regulating airway inflammation. When Th1 and Th2 cells are transferred together into recipient mice, there is a marked reduction in airway eosinophilia and mucus staining. To address the precise role of Th1 cells, we asked (i), Are Th2-induced responses inhibited by interferon (IFN)-γ? and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-γ? In IFN-γ receptor−/− recipient mice exposed to inhaled antigen, the inhibitory effects of Th1 cells on both airway eosinophilia and mucus production were abolished. In the absence of IFN-γ receptor signaling, Th1 cells induced mucus but not eosinophilia. Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-γ. The blockade of eosinophilia and mucus production by IFN-γ likely occurs through different inhibitory pathways that are activated downstream of Th2 cytokine secretion and require IFN-γ signaling in tissue of recipient mice.