IL-13 is a therapeutic target in radiation lung injury.
IL-13 is a therapeutic target in radiation lung injury.
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DOI：
10.1038/srep39714
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发表时间：
2016-12-22
影响因子：
4.6
通讯作者：
Citrin DE
中科院分区：
文献类型：
--
作者：
Chung SI;Horton JA;Ramalingam TR;White AO;Chung EJ;Hudak KE;Scroggins BT;Arron JR;Wynn TA;Citrin DE
肺纤维化是胸部放射治疗的一种潜在致命的晚期不良事件。先前的研究表明，不受限制的TGF-β1和/或2型酪氨酸驱动的免疫应答促进放射损伤后的纤维化，但控制这种病理学的全部因素仍不清楚。白细胞介素13（IL-13）是与蠕虫感染相关的纤维化疾病的关键因素，但目前尚不清楚它是否在辐射诱导的肺纤维化中发挥类似的作用。使用小鼠模型，我们测试了IL-13驱动辐射诱导的肺纤维化进展的假设。来自野生型c57 BL/6 NcR小鼠的辐照肺积累了交替激活的巨噬细胞，显示IL-13水平升高和广泛的纤维化，而IL-13缺陷小鼠对这些变化具有抗性。此外，辐照野生型小鼠的血浆显示循环诱饵受体IL-13 R α2的IL-13饱和部分一过性增加。最后，我们确定在IL-13 R α2饱和期间，IL-13的治疗性中和足以保护小鼠免受肺纤维化。总之，我们的研究结果表明，IL-13是辐射诱导的肺损伤的主要调节因子，并表明，重点关注IL-13的策略可能有助于筛选及时提供抗IL-13治疗。
Pulmonary fibrosis is a potentially lethal late adverse event of thoracic irradiation. Prior research indicates that unrestrained TGF-β1 and/or type 2 cytokine-driven immune responses promote fibrosis following radiation injury, but the full spectrum of factors governing this pathology remains unclear. Interleukin 13 (IL-13) is a key factor in fibrotic disease associated with helminth infection, but it is unclear whether it plays a similar role in radiation-induced lung fibrosis. Using a mouse model, we tested the hypothesis that IL-13 drives the progression of radiation-induced pulmonary fibrosis. Irradiated lungs from wild-type c57BL/6NcR mice accumulated alternatively-activated macrophages, displayed elevated levels of IL-13, and extensive fibrosis, whereas IL-13 deficient mice were resistant to these changes. Furthermore, plasma from irradiated wild-type mice showed a transient increase in the IL-13 saturated fraction of the circulating decoy receptor IL-13Rα2. Finally, we determined that therapeutic neutralization of IL-13, during the period of IL-13Rα2 saturation was sufficient to protect mice from lung fibrosis. Taken together, our results demonstrate that IL-13 is a major regulator of radiation-induced lung injury and demonstrates that strategies focusing on IL-13 may be useful in screening for timely delivery of anti-IL-13 therapeutics.