Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells.

Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells.
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DOI:
10.1038/ni.3308
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发表时间:
2016-01
期刊:
影响因子:
30.5
通讯作者:
Fritz, Joerg H.
Fritz, Joerg H.
中科院分区:
医学1区
文献类型:
--
作者:
Duerr, Claudia U.;McCarthy, Connor D. A.;Mindt, Barbara C.;Rubio, Manuel;Meli, Alexandre P.;Pothlichet, Julien;Eva, Megan M.;Gauchat, Jean-Francois;Qureshi, Salman T.;Mazer, Bruce D.;Mossman, Karen L.;Malo, Danielle;Gamero, Ana M.;Vidal, Silvia M.;King, Irah L.;Sarfati, Marika;Fritz, Joerg H.

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病毒呼吸道感染是感染引起的哮喘和哮喘加重的主要原因,目前仍无法从机制上解释这些原因。在这里,我们发现I型干扰素受体信号的缺失导致了第二组固有淋巴样细胞(ILC2细胞)的非调控激活和感染相关的2型免疫病理。I型干扰素以依赖于转录激活剂ISGF3的方式直接和负面调节小鼠和人类ILC2细胞,导致细胞因子产生改变、细胞增殖和细胞死亡增加。此外,干扰素-γ(干扰素-γ)和白介素27(IL-27)依赖于转录因子STAT1改变了ILC2的功能。这些结果表明,I型和II型干扰素与IL-27一起调节ILC2细胞以限制II型免疫病理。
Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.
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