@article{01GTV28XNHSAJX7B9101FX42Q9,
  abstract     = {{Background: IL-33 plays a major role in the pathogenesis of allergic diseases such as asthma and atopic dermatitis. Upon its release from lung epithelial cells, IL-33 primarily drives type 2 immune responses, accompanied by eosinophilia and robust production of IL-4, IL-5 and IL-13. However, several studies show that IL-33 can also drive a type 1 immune response.
Objective: Important questions remain regarding the mechanisms that determine whether IL-33 induces a type 1 or type 2 immune response. Here we focus on the role of A20 in the regulation of IL-33 signalling in macrophages and IL-33-induced lung immunity.
Methods: We studied the immunological response in lungs of IL-33-treated mice that specifically lack A20 in myeloid cells. We also analysed IL-33 signalling in A20-deficient bone marrow derived macrophages.
Results: IL-33-induced lung ILC2 expansion, type 2 cytokine production and eosinophilia was drastically reduced in the absence of macrophage A20 expression, while neutrophils and interstitial macrophages in lung were increased. In vitro, IL-33-mediated NF-kB activation was only weakly affected in A20-deficient macrophages. However, in the absence of A20, IL-33 gained the ability to activate STAT1 signalling and STAT1-dependent gene expression. Surprisingly, A20-deficient macrophages produced IFN-gamma in response to IL-33, which was fully STAT1-dependent. Furthermore, STAT1 deficiency partially restored the ability of IL-33 to induce ILC2 expansion and eosinophilia in myeloid cell-specific A20 knockout mice. 
Conclusion: We reveal a novel role for A20 as a negative regulator of IL-33-induced STAT1 signalling and IFN-gamma production in macrophages, which determines lung immune responses.
Clinical implications: Our findings may eventually help to identify strategies that allow a better stratification of patients, leading to enhanced treatment efficacy.}},
  author       = {{Holgado Muñoz, Aurora and Liu, Zhuangzhuang and Aidarova, Aigerim and Müller, Christina and Haegman, Mira and Driege, Yasmine and Kreike, Marja and Scott, Charlotte and Afonina, Inna and Beyaert, Rudi}},
  issn         = {{0091-6749}},
  journal      = {{JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}},
  keywords     = {{autoimmunity,allergic asthma,eosinophilia,airway inflammation,IFN-gamma,mouse models,macrophages,TNFAIP3,IL-33}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{244--256.e4}},
  title        = {{A20 is a master switch of IL-33 signalling in macrophages and determines IL-33-induced lung immunity}},
  url          = {{http://doi.org/10.1016/j.jaci.2023.02.026}},
  volume       = {{152}},
  year         = {{2023}},
}

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