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

Abstract

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.

• Authors: Korneliusz Golebski, Xavier R Ros, Maho Nagasawa, Sophie van Tol, Balthasar A Heesters, Hajar Aglmous, Chantal M A Kradolfer, Medya M Shikhagaie, Sven Seys, P W Hellings, Cornelis M van Drunen, Wytske J Fokkens, Hergen Spits, Suzanne M Bal
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 2162 (05 14 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31089134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL17A protein, human
• Interleukin-17
• Interleukin-1beta
• Interleukin-23

Topics

• Adult
• Animals
• Cell Line
• Cell Plasticity (immunology)
• Cystic Fibrosis (blood, immunology, pathology)
• Female
• Humans
• Immunity, Innate
• Inflammation (blood, immunology, pathology)
• Interleukin-17 (immunology, metabolism)
• Interleukin-1beta (immunology, metabolism)
• Interleukin-23 (immunology, metabolism)
• Male
• Mice
• Middle Aged
• Nasal Mucosa (cytology, immunology, pathology)
• Nasal Polyps (blood, immunology, pathology)
• Neutrophils (immunology)
• Th17 Cells (immunology)
• Young Adult