Target and Translational Science, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Center for Infectious Medicine, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
Eur J Immunol. 2019 Jun;49(6):884-893. doi: 10.1002/eji.201848006. Epub 2019 Mar 28.
Human type 2 innate lymphoid cells (ILC2) are the only ILC subset that shows heterogeneous expression of the SCF receptor c-Kit (CD117). Despite its use as surface marker to distinguish ILC populations, its influence on ILC2 biology has not been investigated. Here, we show that c-Kit expression of peripheral blood ILC distinguishes two functionally distinct ILC2 subsets (c-Kit and c-Kit ). When examined for their potential for functional plasticity we found that c-Kit ILC2 displayed greater potential to produce type 2 cytokines, possibly representing fully mature and lineage committed ILC2. On the other hand, c-Kit ILC2 coexpressed the ILC3-marker and chemokine receptor CCR6 and were able to mount a significant IL-17A response under ILC3-promoting conditions. In addition, c-Kit ILC2 produced higher levels of IFN-γ than c-Kit ILC2 under ILC1-conditions. Although costimulation with SCF did not further influence ILC2 plasticity, it augmented type 2 cytokine production. We conclude that c-Kit marks distinct subpopulations of ILC2, which has therapeutic implications for conditions in which ILC2 are involved, such as allergy and asthma.
人类 2 型先天淋巴样细胞（ILC2）是唯一表现出干细胞因子受体 c-Kit（CD117）异质性表达的 ILC 亚群。尽管它被用作区分 ILC 群体的表面标记物，但它对 ILC2 生物学的影响尚未得到研究。在这里，我们表明外周血 ILC 中的 c-Kit 表达可区分两种功能不同的 ILC2 亚群（c-Kit 和 c-Kit ）。当研究它们的功能可塑性潜力时，我们发现 c-Kit ILC2 显示出产生 2 型细胞因子的更大潜力，可能代表完全成熟和谱系定型的 ILC2。另一方面，c-Kit ILC2 共表达 ILC3 标志物和趋化因子受体 CCR6，并且在 ILC3 促进条件下能够产生显著的 IL-17A 反应。此外，在 ILC1 条件下，c-Kit ILC2 产生的 IFN-γ 水平高于 c-Kit ILC2。尽管 SCF 的共刺激作用并未进一步影响 ILC2 的可塑性，但它增强了 2 型细胞因子的产生。我们得出结论，c-Kit 标记了 ILC2 的不同亚群，这对涉及 ILC2 的疾病具有治疗意义，例如过敏和哮喘。
