Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Location AMC, Meibergdreef 9, Amsterdam, 1105, AZ, The Netherlands.
Department of Immunology and Microbiology, Lab of Clinical Immunology, KU Leuven, Belgium Herestraat 49-box 1030, BE-3000, Leuven, Belgium.
Nat Commun. 2019 May 14;10(1):2162. doi: 10.1038/s41467-019-09883-7.
Innate lymphoid cells (ILCs) are crucial for the immune surveillance at mucosal sites. ILCs coordinate early eradication of pathogens and contribute to tissue healing and remodeling, features that are dysfunctional in patients with cystic fibrosis (CF). The mechanisms by which ILCs contribute to CF-immunopathology are ill-defined. Here, we show that group 2 ILCs (ILC2s) transdifferentiated into IL-17-secreting cells in the presence of the epithelial-derived cytokines IL-1β, IL-23 and TGF-β. This conversion is abrogated by IL-4 or vitamin D3. IL-17 producing ILC2s induce IL-8 secretion by epithelial cells and their presence in nasal polyps of CF patients is associated with neutrophilia. Our data suggest that ILC2s undergo transdifferentiation in CF nasal polyps in response to local cytokines, which are induced by infectious agents.
先天淋巴细胞（ILCs）对于粘膜部位的免疫监视至关重要。ILCs 协调早期清除病原体，并有助于组织愈合和重塑，而囊性纤维化（CF）患者的这些功能失调。ILCs 促进 CF 免疫病理学的机制尚不清楚。在这里，我们表明，在上皮衍生细胞因子 IL-1β、IL-23 和 TGF-β 的存在下，第 2 组 ILC（ILC2）向 IL-17 分泌细胞转化。IL-4 或维生素 D3 可阻断这种转化。产生 IL-17 的 ILC2 通过诱导上皮细胞分泌 IL-8，并在 CF 患者的鼻息肉中存在与嗜中性粒细胞增多相关。我们的数据表明，ILC2 在 CF 鼻息肉中发生转化，以响应由感染因子诱导的局部细胞因子。
