IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs.
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.
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Suzanne M
SM
Bal
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Jochem H
JH
Bernink
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Maho
M
Nagasawa
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Jelle
J
Groot
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Medya M
MM
Shikhagaie
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.|Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
Kornel
K
Golebski
Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
Cornelis M
CM
van Drunen
Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.|Department of Pulmonology, Academic Medical Center, Amsterdam, the Netherlands.
Rene
R
Lutter
Department of Pulmonology, Academic Medical Center, Amsterdam, the Netherlands.
Rene E
RE
Jonkers
Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
Pleun
P
Hombrink
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Melanie
M
Bruchard
Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands.
Julien
J
Villaudy
Department of Hematology, Academic Medical Center, Amsterdam, the Netherlands.
J Marius
JM
Munneke
Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
Wytske
W
Fokkens
Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Jonas S
JS
Erjefält
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Hergen
H
Spits
Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
Xavier Romero
XR
Ros
D000818:Animals; D002454:Cell Differentiation; D000066670:Cell Plasticity; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009298:Nasal Polyps / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology
D053583:Interleukin-1beta; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma