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Campylobacter infection promotes IFNγ-dependent intestinal pathology via ILC3 to ILC1 conversion
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-11-19 , DOI: 10.1038/s41385-020-00353-8
Wayne T Muraoka 1, 2, 3 , Anna A Korchagina 1 , Qingqing Xia 2, 4 , Sergey A Shein 1 , Xi Jing 1 , Zhao Lai 5, 6 , Korri S Weldon 5 , Li-Ju Wang 5 , Yidong Chen 5 , Lawrence W Kummer 2 , Markus Mohrs 2, 7 , Eric Vivier 8 , Ekaterina P Koroleva 1 , Alexei V Tumanov 1
Affiliation  

Innate lymphoid cells (ILCs) are a heterogeneous family of immune regulators that protect against mucosal pathogens but can also promote intestinal pathology. Although the plasticity between ILCs populations has been described, the role of mucosal pathogens in inducing ILC conversion leading to intestinal pathology remains unclear. Here we demonstrate that IFNγ-producing ILCs are responsible for promoting intestinal pathology in a mouse model of enterocolitis caused by Campylobacter jejuni, a common human enteric pathogen. Phenotypic analysis revealed a distinct population of IFNγ-producing NK1.1T-bet+ILCs that accumulated in the intestine of C. jejuni-infected mice. Adoptive transfer experiments demonstrated their capacity to promote intestinal pathology. Inactivation of T-bet in NKp46+ ILCs ameliorated disease. Transcriptome analysis and cell-fate mapping experiments revealed that IFNγ-producing NK1.1ILCs correspond to ILC1 profile and develop from RORγt+ progenitors. Collectively, we identified a distinct population of NK1.1ex-ILC3s that promotes intestinal pathology through IFNγ production in response to C. jejuni infection.



中文翻译:

弯曲杆菌感染通过 ILC3 向 ILC1 的转化促进 IFNγ 依赖性肠道病理学

先天性淋巴样细胞 (ILC) 是免疫调节剂的异质家族,可防止粘膜病原体,但也可促进肠道病理。尽管已经描述了 ILC 种群之间的可塑性,但粘膜病原体在诱导 ILC 转化导致肠道病理学方面的作用仍不清楚。在这里,我们证明产生 IFNγ 的 ILC 负责促进由空肠弯曲杆菌(一种常见的人类肠道病原体)引起的小肠结肠炎小鼠模型的肠道病理学。表型分析揭示了一个独特的产生 IFNγ 的 NK1.1 T-bet + ILCs 群体在空肠弯曲杆菌的肠道中积累- 感染小鼠。过继转移实验证明了它们促进肠道病理学的能力。NKp46 + ILC 中 T-bet 的失活改善了疾病。转录组分析和细胞命运图谱实验表明,产生 IFNγ 的 NK1.1 ILC 对应于 ILC1 谱并从 RORγt +祖细胞发育而来。总的来说,我们确定了一个独特的 NK1.1 - ex-ILC3 群体,通过产生 IFNγ 来响应空肠弯曲杆菌感染,从而促进肠道病理学。

更新日期:2020-11-19
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