Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells.
Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells.
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DOI：
10.1084/jem.20071840
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发表时间：
2008-03-17
影响因子：
15.3
通讯作者：
Lee, James J.
中科院分区：
文献类型：
--
作者：
Jacobsen, Elizabeth A.;Ochkur, Sergei I.;Pero, Ralph S.;Taranova, Anna G.;Protheroe, Cheryl A.;Colbert, Dana C.;Lee, Nancy A.;Lee, James J.
当前围绕肺部中变应原介导的辅助性T细胞2型（Th 2）免疫应答的范例表明T细胞几乎占据主导地位。我们的研究提出了另一种假设，即嗜酸性粒细胞参与调节肺T细胞反应。特别是，卵清蛋白（OVA）致敏/激发的小鼠缺乏嗜酸性粒细胞（转基因系PHIL）有减少的气道水平的Th 2细胞因子相对于OVA治疗的野生型，这与减少的能力募集效应T细胞到肺。将Th 2极化的OVA特异性转基因T细胞（OT-II）单独连续转移到OVA攻击的PHIL受体小鼠中未能恢复Th 2细胞因子、气道组织病理学，最重要的是，肺效应T细胞的募集。相比之下，OT-II细胞和嗜酸性粒细胞联合转移到PHIL小鼠中导致效应T细胞的积累以及气道Th 2免疫应答和组织病理学的伴随增加。此外，我们发现，嗜酸性粒细胞引起的Th 2趋化因子的表达胸腺和活化调节趋化因子/CCL 17和巨噬细胞衍生的趋化因子/CCL 22在肺过敏原的挑战后，这些趋化因子的封锁抑制效应T细胞的招聘。总之，这些数据表明，肺嗜酸性粒细胞是局部募集效应T细胞所必需的。
The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.
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白介素5缺乏消除小鼠哮喘模型中的嗜酸性粒细胞，气道高反应性和肺损伤。
影响因子：
15.3
作者：
Foster, PS;Hogan, SP;Ramsay, AJ;Matthaei, KI;Young, IG
通讯作者：
Young, IG
影响因子：
14.2
作者：
Duez, C;Dakhama, A;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
20.3
作者：
Kim, CH;Johnston, B;Butcher, EC
通讯作者：
Butcher, EC
DOI：
10.1073/pnas.0607863103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Fulkerson, Patricia C.;Fischetti, Christine A.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
14.2
作者：
Gelfand, EW;Dakhanna, A
通讯作者：
Dakhanna, A