IL-33 dysregulates regulatory T (Treg) cells and impairs established immunological tolerance in the lungs

Publication date: Available online 11 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Chien-Chang Chen, Takao Kobayashi, Koji Iijima, Fan-Chi Hsu, Hirohito Kita
BackgroundAirway exposure to environmental antigens generally leads to immunological tolerance. A fundamental question remains: why is airway tolerance compromised in patients with allergic airway diseases? Interleukin (IL)-33 promotes innate and adaptive type 2 immunity and may provide the answer to this question.ObjectiveThe goal of this study was to investigate the roles IL-33 plays in altering regulatory T (Treg) cells in the lungs and in affecting previously established airway immunological tolerance.MethodsWe analyzed CD4⁺ forkhead box p3 (Foxp3)⁺ Treg cells that were isolated from the lungs of naïve BALB/c mice and those treated with IL-33. Airway tolerance and allergen-induced airway inflammation models in mice were used to investigate how IL-33 affects established immunological tolerance in vivo.ResultsCD4⁺Foxp3⁺ Treg cells in the lungs expressed IL-33 receptor ST2. When exposed to IL-33, Treg cells upregulated their expression of canonical Th2 transcription factor GATA3 as well as ST2, and produced type 2 cytokines. Treg cells lost their ability to suppress effector T cells in the presence of IL-33. Airway administration of IL-33 with an antigen impaired the immunological tolerance in the lungs that had been established by prior exposure to the antigen. Dysregulated Foxp3⁺ Treg cells with distinct characteristics of Th2 cells increased in the lungs of the mice undergoing IL-33-dependent allergen-driven airway inflammation.ConclusionsIL-33 dysregulated lung Treg cells and impaired immunological tolerance to inhaled antigens. Established airway tolerance may not be sustained in the presence of an innate immunological stimulation, such as IL-33.

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Teaser

Using mouse models, Chen et al. showed that IL-33 dysregulated Treg cells in the lungs of mice toward a "Th2 cell-like" phenotype and impaired established immunological tolerance in the lungs.


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