Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX, USA.
Trudeau Institute, Saranac Lake, NY, USA.
Mucosal Immunol. 2021 May;14(3):703-716. doi: 10.1038/s41385-020-00353-8. Epub 2020 Nov 19.
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-betILCs 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.
先天淋巴细胞（ILCs）是一类具有异质性的免疫调节细胞，它们可以抵御黏膜病原体，但也可能促进肠道病理。虽然已经描述了 ILCs 群体之间的可塑性，但黏膜病原体在诱导 ILC 转化导致肠道病理方面的作用仍不清楚。在这里，我们证明了 IFNγ 产生的 ILCs 在由空肠弯曲菌（一种常见的人类肠道病原体）引起的结肠炎小鼠模型中负责促进肠道病理。表型分析显示，在空肠弯曲菌感染的小鼠肠道中积累了一种独特的 IFNγ 产生的 NK1.1T-betILCs 群体。过继转移实验证明了它们促进肠道病理的能力。在 NKp46 ILCs 中失活 T-bet 可改善疾病。转录组分析和细胞命运图谱实验表明，IFNγ 产生的 NK1.1ILCs 对应于 ILC1 特征，并由 RORγt 祖细胞发育而来。总之，我们鉴定了一种独特的 NK1.1ex-ILC3 群体，它通过对空肠弯曲菌感染的 IFNγ 产生促进肠道病理。
