英国弗朗西斯·克里克研究所Andreas Wack课题组近日取得一项新成果。他们发现在病毒感染恢复过程中，I型（IFN-α/β）和III型（IFN-λ）干扰素干扰肺上皮修复。2020年6月11日出版的《科学》杂志发表了这项成果。

他们显示IFN信号传导在流感恢复期间干扰了肺修复，其中IFN-λ最有效地驱动了这些作用。 IFN诱导的p53直接降低上皮的增殖和分化，增加疾病的严重性，并增加细菌感染的易感性。因此，过量或长时间的IFN产生会通过损害肺上皮再生来加重病毒感染。

因而，时间和持续时间是内源性IFN作用的关键参数，对于针对诸如流感和冠状病毒病2019（COVID-19）等病毒感染的IFN治疗策略，应谨慎考虑。

据介绍，过度的细胞因子信号传导经常在呼吸道病毒感染期间加剧肺组织损伤。IFN-α/β和III型IFN-λ干扰素是宿主产生的抗病毒细胞因子。延长的IFN-α/β反应可导致有害的促炎作用，而IFN-λ主要在上皮细胞中发出信号，从而诱导局部抗病毒免疫。

Author: Jack Major, Stefania Crotta, Miriam Llorian, Teresa M. McCabe, Hans Henrik Gad, Simon L. Priestnall, Rune Hartmann, Andreas Wack

Issue&Volume: 2020/06/11

Abstract: Abstract Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-α/β) and III (IFN-λ) interferons are host-produced antiviral cytokines. Prolonged IFN-α/β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, inducing localized antiviral immunity. Here we show that IFN signaling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity, and susceptibility to bacterial superinfections. Thus, excessive or prolonged IFN-production aggravates viral infection by impairing lung epithelial regeneration. Therefore, timing and duration are critical parameters of endogenous IFN action and should be considered carefully for IFN therapeutic strategies against viral infections like influenza and coronavirus disease 2019 (COVID-19).

DOI: 10.1126/science.abc2061

Source: https://science.sciencemag.org/content/early/2020/06/10/science.abc2061