Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
Nat Immunol. 2016 Jun;17(6):636-45. doi: 10.1038/ni.3444. Epub 2016 Apr 25.
Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.
2 型固有淋巴细胞（ILC2s）分泌 2 型细胞因子，可抵御寄生虫，但也可导致多种炎症性气道疾病。我们在此报告，白细胞介素 1β（IL-1β）可直接激活人 ILC2s，而 IL-12 诱导这些激活的 ILC2 转化为产生干扰素-γ（IFN-γ）的 ILC1s，IL-4 可逆转这一过程。ILC 的可塑性表现在患有严重慢性阻塞性肺疾病（COPD）或慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的患者的病变组织中，这些组织分别显示出 IL-12 或 IL-4 特征，并积累了 ILC1s 或 ILC2s。嗜酸性粒细胞是 IL-4 的主要细胞来源，这揭示了产生 IL-5 的 ILC2s 和产生 IL-4 的嗜酸性粒细胞之间的交叉对话。我们提出，IL-12 和 IL-4 控制 ILC2 的功能特性，其失衡导致 1 型或 2 型炎症的持续存在。
