Trefoil Factor 2 Promotes Type 2 Immunity and Lung Repair through Intrinsic Roles in Hematopoietic and Nonhematopoietic Cells
Trefoil Factor 2 Promotes Type 2 Immunity and Lung Repair through Intrinsic Roles in Hematopoietic and Nonhematopoietic Cells
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DOI：
10.1016/j.ajpath.2018.01.020
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发表时间：
2018-05-01
影响因子：
6
通讯作者：
Herbert, De'Broski R.
中科院分区：
文献类型：
--
作者：
Hung, Li-Yin;Oniskey, Taylor K.;Herbert, De'Broski R.
三叶因子（IFFs）是一种小的分泌性蛋白质，调节组织的完整性和粘膜表面的修复，特别是在胃肠道。然而，它们对控制基线肺功能或感染引起的肺损伤程度的相对贡献尚不清楚。使用辐射骨髓嵌合体，我们发现，TFF2产生的造血和非造血来源的细胞是必不可少的宿主保护，肺泡2型细胞的增殖，并恢复与钩虫寄生虫Nippostrongylus brosiliensis感染后的肺部气体交换。在没有TFF2的情况下，肺上皮细胞不能增殖，并且在感染性损伤后表达降低的肺2型应答诱导IL-25和IL-33的mRNA转录水平。引人注目的是，即使在没有感染或辐射的情况下，TFF2缺乏也损害肺结构和功能，其特征在于相对于野生型对照小鼠肺泡扩张和血氧水平降低。两者合计，我们显示了一个以前不受重视的作用TFF2，产生的造血或非造血来源，作为一个促增殖因子的肺上皮细胞在稳态和感染性损伤条件下。
Trefoil factors (IFFs) are small secreted proteins that regulate tissue integrity and repair at mucosal surfaces, particularly in the gastrointestinal tract. However, their relative contribution(s) to controlling baseline lung function or the extent of infection-induced lung injury are unknown issues. With the use of irradiation bone marrow chimeras, we found that TFF2 produced from both hematopoietic- and nonhematopoietic-derived cells is essential for host protection, proliferation of alveolar type 2 cells, and restoration of pulmonary gas exchange after infection with the hookworm parasite Nippostrongylus brosiliensis. In the absence of TFF2, lung epithelia were unable to proliferate and expressed reduced lung mRNA transcript levels for type 2 response-inducing IL-25 and IL-33 after infectious injury. Strikingly, even in the absence of infection or irradiation, TFF2 deficiency compromised lung structure and function, as characterized by distended alveoli and reduced blood oxygen levels relative to wild type control mice. Taken together, we show a previously unappreciated role for TFF2, produced by either hematopoietic or nonhematopoietic sources, as a pro-proliferative factor for lung epithelial cells under steady-state and infectious injury conditions.