TY - JOUR
T1 - IL-1β, IL-23, and TGF-β drive plasticity of human ILC2s towards IL-17-producing ILCs in nasal inflammation
AU - Golebski, Korneliusz
AU - Ros, Xavier R.
AU - Nagasawa, Maho
AU - van Tol, Sophie
AU - Heesters, Balthasar A.
AU - Aglmous, Hajar
AU - Kradolfer, Chantal M. A.
AU - Shikhagaie, Medya M.
AU - Seys, Sven
AU - Hellings, P. W.
AU - van Drunen, Cornelis M.
AU - Fokkens, Wytske J.
AU - Spits, Hergen
AU - Bal, Suzanne M.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065801106&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31089134
U2 - https://doi.org/10.1038/s41467-019-09883-7
DO - https://doi.org/10.1038/s41467-019-09883-7
M3 - Article
C2 - 31089134
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2162
ER -