IL-33 Precedes IL-5 in Regulating Eosinophil Commitment and Is Required for Eosinophil Homeostasis.
IL-33 Precedes IL-5 in Regulating Eosinophil Commitment and Is Required for Eosinophil Homeostasis.
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IL-33先于调节嗜酸性粒细胞承诺的IL-5之前，是嗜酸性粒细胞稳态所必需的。
DOI：
10.4049/jimmunol.1600611
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Bryce PJ
中科院分区：
文献类型：
--
作者：
Johnston LK;Hsu CL;Krier-Burris RA;Chhiba KD;Chien KB;McKenzie A;Berdnikovs S;Bryce PJ
嗜酸性粒细胞在许多疾病的发病机制中是重要的，包括哮喘、嗜酸性食管炎和湿疹。虽然IL-5对于支持成熟的嗜酸性粒细胞至关重要，但支持早期嗜酸性粒细胞谱系事件的信号定义较少。IL-33受体ST 2在包括嗜酸性粒细胞在内的几种炎性细胞上表达，并且最好表征其在外周组织中过敏反应起始期间的作用。最近，ST 2在造血祖细胞亚群上表达，但其功能仍存在争议。我们的研究结果表明，IL-33是基础嗜酸性粒细胞稳态所必需的，因为IL-33和ST 2缺陷小鼠在基线时表现出外周血嗜酸性粒细胞数量减少。外源性IL-33给药增加了WT和IL-33缺陷小鼠骨髓和外周中的成熟嗜酸性粒细胞，但ST 2缺陷小鼠没有。在这种治疗下，全身性IL-5也增加，并且用中和抗体阻断IL-5消除了IL-33诱导的成熟嗜酸性粒细胞扩增。在IL-5转基因小鼠中观察到的稳态嗜酸性粒细胞增多症在ST 2缺乏时显著降低，尽管全身IL-5升高相似。最后，在体外用IL-33而不是IL-5处理骨髓细胞，导致表达IL-5 R α的前体细胞特异性早期扩增。总之，我们的研究结果确立了IL-33和ST 2缺陷小鼠嗜酸性粒细胞生成的基础缺陷，以及IL-33通过驱动全身IL-5产生和表达IL-5 R α的前体细胞扩增来支持成熟嗜酸性粒细胞的机制。
Eosinophils are important in the pathogenesis of many diseases, including asthma, eosinophilic esophagitis, and eczema. While IL-5 is crucial for supporting mature eosinophils, the signals that support earlier eosinophil lineage events are less defined. The IL-33 receptor, ST2, is expressed on several inflammatory cells, including eosinophils, and is best characterized for its role during the initiation of allergic responses in peripheral tissues. Recently, ST2 expression was described on hematopoietic progenitor subsets, where its function remains controversial. Our findings demonstrate that IL-33 is required for basal eosinophil homeostasis, since both IL-33– and ST2-deficient mice exhibited diminished peripheral blood eosinophil numbers at baseline. Exogenous IL-33 administration increased mature eosinophils in both the bone marrow and periphery in WT and IL-33–deficient, but not ST2-deficient, mice. Systemic IL-5 was also increased under this treatment, and blocking IL-5 with a neutralizing antibody ablated of the IL-33-induced mature eosinophil expansion. The homeostatic hypereosinophilia seen in IL-5–transgenic mice was significantly lower with ST2 deficiency despite similar elevations in systemic IL-5. Finally, in vitro treatment of bone marrow cells with IL-33, but not IL-5, led to specific early expansion of IL-5Rα–expressing precursor cells. In summary, our findings establish a basal defect in eosinophilopoiesis in IL-33– and ST2-deficient mice and a mechanism whereby IL-33 supports mature eosinophils by driving both systemic IL-5 production and the expansion of IL-5Rα–expressing precursor cells.
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影响因子：
32.4
作者：
Kopf, M;Brombacher, F;Matthaei, KI
通讯作者：
Matthaei, KI
DOI：
10.1164/rccm.201201-0134oc
发表时间：
2012-08-01
影响因子：
24.7
作者：
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4.4
作者：
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通讯作者：
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影响因子：
14.2
作者：
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通讯作者：
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