Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Immunity. 2013 Apr 18;38(4):769-81. doi: 10.1016/j.immuni.2013.02.010. Epub 2013 Feb 28.
Mucosal innate lymphoid cell (ILC) subsets promote immune responses to pathogens by producing distinct signature cytokines in response to changes in the cytokine microenvironment. We previously identified human ILC3 distinguished by interleukin-22 (IL-22) secretion. Here we characterized a human ILC1 subset that produced interferon-γ (IFN-γ) in response to IL-12 and IL-15 and had a unique integrin profile, intraepithelial location, hallmarks of TGF-β imprinting, and a memory-activated phenotype. Because tissue-resident memory CD8(+) T cells share this profile, intraepithelial ILC1 may be their innate counterparts. In mice, intraepithelial ILC1 were distinguished by CD160 expression and required Nfil3- and Tbx21-encoded transcription factors for development, but not IL-15 receptor-α, indicating that intraepithelial ILC1 are distinct from conventional NK cells. Intraepithelial ILC1 were amplified in Crohn's disease patients and contributed to pathology in the anti-CD40-induced colitis model in mice. Thus, intraepithelial ILC1 may initiate IFN-γ responses against pathogens but contribute to pathology when dysregulated.
黏膜固有淋巴细胞 (ILC) 亚群通过响应细胞因子微环境的变化产生独特的特征性细胞因子，从而促进对病原体的免疫反应。我们之前鉴定出了人 ILC3，其特征是分泌白细胞介素-22 (IL-22)。在这里，我们描述了一个人类 ILC1 亚群，该亚群在受到 IL-12 和 IL-15 的刺激后会产生干扰素-γ (IFN-γ)，并且具有独特的整合素特征、上皮内位置、TGF-β印迹的特征以及记忆激活表型。由于组织驻留记忆 CD8(+)T 细胞具有这种特征，上皮内 ILC1 可能是它们的先天对应物。在小鼠中，上皮内 ILC1 通过 CD160 表达来区分，并且其发育需要 Nfil3 和 Tbx21 编码的转录因子，但不需要 IL-15 受体-α，表明上皮内 ILC1 与传统 NK 细胞不同。上皮内 ILC1 在克罗恩病患者中扩增，并在小鼠抗 CD40 诱导的结肠炎模型中导致病理学改变。因此，上皮内 ILC1 可能会引发针对病原体的 IFN-γ 反应，但在失调时会导致病理学改变。
