Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London NW7 1AA, England, UK.
J Exp Med. 2013 Dec 16;210(13):2951-65. doi: 10.1084/jem.20130071. Epub 2013 Nov 18.
IL-9 fate reporter mice established type 2 innate lymphoid cells (ILC2s) as major producers of this cytokine in vivo. Here we focus on the role of IL-9 and ILC2s during the lung stage of infection with Nippostrongylus brasiliensis, which results in substantial tissue damage. IL-9 receptor (IL-9R)-deficient mice displayed reduced numbers of ILC2s in the lung after infection, resulting in impaired IL-5, IL-13, and amphiregulin levels, despite undiminished numbers of Th2 cells. As a consequence, the restoration of tissue integrity and lung function was strongly impaired in the absence of IL-9 signaling. ILC2s, in contrast to Th2 cells, expressed high levels of the IL-9R, and IL-9 signaling was crucial for the survival of activated ILC2s in vitro. Furthermore, ILC2s in the lungs of infected mice required the IL-9R to up-regulate the antiapoptotic protein BCL-3 in vivo. This highlights a unique role for IL-9 as an autocrine amplifier of ILC2 function, promoting tissue repair in the recovery phase after helminth-induced lung inflammation.
IL-9 命运报告小鼠将 2 型固有淋巴细胞 (ILC2) 确立为体内这种细胞因子的主要产生者。在这里，我们关注 IL-9 和 ILC2 在感染巴西旋毛虫的肺部阶段的作用，这会导致大量组织损伤。IL-9 受体 (IL-9R) 缺陷型小鼠在感染后肺部的 ILC2 数量减少，导致 IL-5、IL-13 和 Amphiregulin 水平降低，尽管 Th2 细胞数量没有减少。因此，在没有 IL-9 信号的情况下，组织完整性和肺功能的恢复受到严重损害。与 Th2 细胞相反，ILC2 表达高水平的 IL-9R，IL-9 信号对于体外激活的 ILC2 的存活至关重要。此外，感染小鼠肺部的 ILC2 需要 IL-9R 在体内上调抗凋亡蛋白 BCL-3。这突出了 IL-9 作为 ILC2 功能的自分泌放大器的独特作用，促进了寄生虫诱导的肺部炎症恢复阶段的组织修复。
