Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus.
Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus.
复制标题
DOI：
10.4049/jimmunol.1602009
复制
发表时间：
2017-04-15
期刊：
影响因子：
--
通讯作者：
Sun XH
中科院分区：
文献类型：
--
作者：
Wang HC;Qian L;Zhao Y;Mengarelli J;Adrianto I;Montgomery CG;Urban JF Jr;Fung KM;Sun XH
先天性淋巴样细胞（inate lymphoid cells，ILC）是多种免疫应答的重要调节者。目前的范式表明，所有新产生的ILC都来源于骨髓中的共同淋巴祖细胞（CLP）。Id2是E蛋白转录因子的抑制因子，在ILC分化过程中起重要作用。出乎意料的是，我们发现异位表达Id1或删除胸腺中的两个E蛋白基因大大增加了ILC2在胸腺和ILC2通常驻留的其他器官中的计数。进一步的证据表明这些突变ILC2的胸腺起源。突变小鼠表现出增强的嗜酸性粒细胞的自发浸润和增强的反应，木瓜蛋白酶在肺和增强的能力，驱逐蠕虫寄生虫，日本圆线虫巴西。这些结果提示了一个问题，即胸腺是否天然具有产生ILC2的能力，而E蛋白抑制了这种潜力。Id1转基因小鼠中ILC2的丰富也为测试ILC2的生物学功能提供了独特的机会。
Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Unexpectedly, we found that ectopically expressing Id1 or deleting two E protein genes in the thymus drastically increased ILC2 counts in the thymus and other organs where ILC2 normally reside. Further evidence suggests a thymic origin of these mutant ILC2s. The mutant mice exhibit augmented spontaneous infiltration of eosinophils and heightened responses to papain in the lung and increased ability to expulse the helminth parasite, Nippostrongylus brasiliensis. These results prompt the question whether the thymus naturally has the capacity to produce ILC2s and E proteins restrain such a potential. The abundance of ILC2s in Id1 transgenic mice also offers a unique opportunity for testing the biological functions of ILC2s.