IL-33-activated dendritic cells are critical for allergic airway inflammation
IL-33-activated dendritic cells are critical for allergic airway inflammation
复制标题
DOI：
10.1002/eji.201041033
复制
发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Ryffel, Bernhard
中科院分区：
文献类型：
--
作者：
Besnard, Anne-Gaelle;Togbe, Dieudonnee;Ryffel, Bernhard
IL-33是IL-1家族细胞因子的新成员，参与多种疾病中的Th 2型应答，并通过许多免疫细胞上表达的ST 2受体发出信号。由于IL-33对DC的作用仍然存在争议，我们研究了IL-33在体外和体内调节DC功能的能力。在这里，我们报道IL-33激活髓样DC产生IL-6、IL-1 β、TNF、CCL 17并表达高水平的CD 40、CD 80 OX 40 L和CCR 7。重要的是，IL-33激活的DC引发幼稚淋巴细胞产生Th 2细胞因子IL-5和IL-13，但不产生IL-4。在体内，IL-33暴露诱导肺中的DC募集和活化。使用OVA诱导的过敏性肺部炎症模型，我们证明了ST 2缺陷小鼠气道炎症的减少与DC活化和迁移到引流LN的失败相关。最后，我们发现，过继转移IL-33激活的DC加剧了DC驱动的过敏性气道炎症模型中的肺部炎症。这些数据首次证明IL-33在抗原呈递期间激活DC，从而在变应性肺炎中驱动Th 2型应答。
IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1 beta, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation.