IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs

Suzanne M. Bal, Jochem H. Bernink, Maho Nagasawa, Jelle Groot, Medya M. Shikhagaie, Kornel Golebski, Cornelis M. van Drunen, Rene Lutter, Rene E. Jonkers, Pleun Hombrink, Melanie Bruchard, Julien Villaudy, J. Marius Munneke, Wytske Fokkens, Jonas S. Erjefält, Hergen Spits, Xavier Romero Ros

Research output: Contribution to journalArticleAcademicpeer-review

326 Citations (Scopus)


Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation
Original languageEnglish
Pages (from-to)636-645
JournalNature immunology
Issue number6
Publication statusPublished - 2016

Cite this