Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation.
Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation.
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DOI：
10.1186/1471-2172-13-6
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发表时间：
2012-01-31
期刊：
影响因子：
3
通讯作者：
Keegan AD
中科院分区：
文献类型：
--
作者：
Ford AQ;Dasgupta P;Mikhailenko I;Smith EM;Noben-Trauth N;Keegan AD
白细胞介素 - 4受体α（IL - 4Rα）链具有广泛的表达模式，并参与白细胞介素 - 4和白细胞介素 - 13的信号传导，从而能够影响过敏性肺部炎症的若干病理成分。我们先前曾报道，骨髓来源细胞和非骨髓来源细胞上的IL - 4Rα表达都会影响过敏性肺部炎症的严重程度。在卵清蛋白激发的小鼠中，表达IL - 4Rα、CD11b和IAd的巨噬细胞数量与嗜酸性粒细胞增多的程度之间存在相关性。白细胞介素 - 4或白细胞介素 - 13与IL - 4Rα结合能够刺激巨噬细胞的替代激活（AAM）。AAM的存在与对寄生虫和过敏原的炎症反应相关。因此，我们假设IL - 4Rα⁺ AAM在过敏性肺部炎症中起积极作用。为了直接确定AAM在过敏性肺部炎症中的作用，从IL - 4Rα阳性和阴性小鼠的骨髓中制备了巨噬细胞集落刺激因子（M - CSF）依赖性巨噬细胞（BMM），并将其转移至IL - 4RαxRAG2⁻/⁻小鼠中。外源性提供野生型辅助性T细胞2（TH2）细胞。
与接受IL - 4Rα⁻/⁻ BMM的小鼠相比，接受IL - 4Rα⁺/⁺ BMM的小鼠在卵清蛋白激发后肺部嗜酸性粒细胞的募集显著增加。正如预期的那样，嗜酸性粒细胞炎症依赖于TH2细胞的存在。此外，我们观察到在接受IL - 4Rα⁺/⁺ BMM的小鼠肺部，表达F4/80和Mac3的细胞以及AAM标志物YM1/2增加。这些小鼠的支气管肺泡灌洗液（BAL）中嗜酸性粒细胞趋化因子 - 1、调节活化正常T细胞表达和分泌因子（RANTES）和趋化因子（CCL2）水平升高。
这些结果表明，IL - 4Rα⁺巨噬细胞的转移足以增强TH2驱动的过敏性炎症。它们进一步表明，通过IL - 4Rα对巨噬细胞的刺激导致其替代激活，并对肺部TH2驱动的过敏性炎症反应产生积极作用。由于在哮喘加重患者中观察到AAM及其产物的增加，这些结果提示AAM可能成为缓解病情加重的靶点。
The IL-4 receptor α (IL-4Rα) chain has a broad expression pattern and participates in IL-4 and IL-13 signaling, allowing it to influence several pathological components of allergic lung inflammation. We previously reported that IL-4Rα expression on both bone marrow-derived and non-bone marrow-derived cells contributed to the severity of allergic lung inflammation. There was a correlation between the number of macrophages expressing the IL-4Rα, CD11b, and IAd, and the degree of eosinophilia in ovalbumin challenged mice. The engagement of the IL-4Rα by IL-4 or IL-13 is able to stimulate the alternative activation of macrophages (AAM). The presence of AAM has been correlated with inflammatory responses to parasites and allergens. Therefore, we hypothesized that IL-4Rα+ AAM play an active role in allergic lung inflammation. To directly determine the role of AAM in allergic lung inflammation, M-CSF-dependent macrophages (BMM) were prepared from the bone-marrow of IL-4Rα positive and negative mice and transferred to IL-4RαxRAG2-/- mice. Wild type TH2 cells were provided exogenously. Mice receiving IL-4Rα+/+ BMM showed a marked increase in the recruitment of eosinophils to the lung after challenge with ovalbumin as compared to mice receiving IL-4Rα-/- BMM. As expected, the eosinophilic inflammation was dependent on the presence of TH2 cells. Furthermore, we observed an increase in cells expressing F4/80 and Mac3, and the AAM marker YM1/2 in the lungs of mice receiving IL-4Rα+/+ BMM. The BAL fluid from these mice contained elevated levels of eotaxin-1, RANTES, and CCL2. These results demonstrate that transfer of IL-4Rα + macrophages is sufficient to enhance TH2-driven, allergic inflammation. They further show that stimulation of macrophages through IL-4Rα leads to their alternative activation and positive contribution to the TH2-driven allergic inflammatory response in the lung. Since an increase in AAM and their products has been observed in patients with asthma exacerbations, these results suggest that AAM may be targeted to alleviate exacerbations.
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影响因子：
8.6
作者：
Chapoval, Svetlana P.;Lee, Chun Geun;Elias, Jack A.
通讯作者：
Elias, Jack A.
DOI：
10.4049/jimmunol.0902185
发表时间：
2010-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Finkelman FD;Hogan SP;Hershey GK;Rothenberg ME;Wills-Karp M
通讯作者：
Wills-Karp M
DOI：
10.1084/jem.187.6.939
发表时间：
1998-03-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kuperman D;Schofield B;Wills-Karp M;Grusby MJ
通讯作者：
Grusby MJ
影响因子：
158.5
作者：
Chupp, Geoffrey L.;Lee, Chun Geun;Elias, Jack A.
通讯作者：
Elias, Jack A.
DOI：
10.1016/j.jaci.2007.10.028
发表时间：
2008-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brightling C;Berry M;Amrani Y
通讯作者：
Amrani Y