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

• Published in: Nature communications Vol. 10; no. 1; pp. 2162 - 15
• Main Authors: Golebski, Korneliusz, Ros, Xavier R., Nagasawa, Maho, van Tol, Sophie, Heesters, Balthasar A., Aglmous, Hajar, Kradolfer, Chantal M. A., Shikhagaie, Medya M., Seys, Sven, Hellings, P. W., van Drunen, Cornelis M., Fokkens, Wytske J., Spits, Hergen, Bal, Suzanne M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.05.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/21; 13/31; 13/95; 38/61; 38/77; 38/90; 631/250/2504/2506; 631/250/256; 631/250/347; 82/1; 82/80; Adult; Animals; Cell Line; Cell Plasticity - immunology; Cystic fibrosis; Cystic Fibrosis - blood; Cystic Fibrosis - immunology; Cystic Fibrosis - pathology; Cytokines; Epithelial cells; Female; Humanities and Social Sciences; Humans; IL-1β; Immunity, Innate; Immunosurveillance; Inflammation - blood; Inflammation - immunology; Inflammation - pathology; Interleukin 17; Interleukin 23; Interleukin 4; Interleukin 8; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Interleukin-23 - immunology; Interleukin-23 - metabolism; Lymphoid cells; Male; Mice; Middle Aged; Mucosal immunity; multidisciplinary; Nasal Mucosa - cytology; Nasal Mucosa - immunology; Nasal Mucosa - pathology; Nasal Polyps - blood; Nasal Polyps - immunology; Nasal Polyps - pathology; Neutrophilia; Neutrophils - immunology; Polyps; Science; Science (multidisciplinary); Th17 Cells - immunology; Vitamin D3; Young Adult
• ISSN: 2041-1723; 2041-1723
• 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. Innate lymphoid cells (ILCs) play critical immunological roles including immune surveillance at mucosal sites. Here the authors show that during nasal inflammation pathogen-induced cytokine production guides the differentiation of ILCs.