IL-1β, IL-23, and TGF-β drive plasticity of human ILC2s towards IL-17-producing ILCs in nasal inflammation

被引：113
作者：
Golebski, Korneliusz [1 ]
Ros, Xavier R. [1 ]
Nagasawa, Maho [1 ]
van Tol, Sophie [1 ]
Heesters, Balthasar A. [1 ]
Aglmous, Hajar [1 ]
Kradolfer, Chantal M. A. [1 ]
Shikhagaie, Medya M. [1 ]
Seys, Sven [2 ]
Hellings, P. W. [2 ]
van Drunen, Cornelis M. [3 ]
Fokkens, Wytske J. [3 ]
Spits, Hergen [1 ]
Bal, Suzanne M. [1 ]
机构：
[1] Univ Amsterdam, Amsterdam UMC, Dept Expt Immunol, Meibergdreef 9, Amsterdam, Netherlands
[2] Katholieke Univ Leuven, Lab Clin Immunol, Dept Immunol & Microbiol, Belgium Herestr 49 Box 1030, B-3000 Leuven, Belgium
[3] Univ Amsterdam, Dept Otorhinolaryngol, Amsterdam UMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
来源：
NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期
基金：
欧洲研究理事会;
关键词：
INNATE LYMPHOID-CELLS; VITAMIN-D DEFICIENCY; CYSTIC-FIBROSIS; T-CELLS; INTERLEUKIN-17; EXACERBATIONS; TRAFFICKING; ASSOCIATION; EXPRESSION; REPRESENTS;
D O I：
10.1038/s41467-019-09883-7
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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-1 beta, IL-23 and TGF-beta. 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.
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页数：15
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