Evidence for an alternative IL13/IL13R mediated allergen response in lung in the absence of ILC2 cells and IL5


Identification: Fraszczak-Jennifer


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Evidence for an alternative IL13/IL13R mediated allergen response in lung in the absence of ILC2 cells and IL5

Jennifer Fraszczak*, Thannina Hamadou and Tarik Möröy*#&

* Institut de recherches cliniques de Montréal, québec, Canada
# Département de microbiologie, infectiologie et immunologie, Faculty of Medicine, Université de Montréal, Montreal, Canada
& Division of Experimental Medicine, McGill University, Montreal, Canada

Asthma is an inflammatory disease of the bronchial airways and is mainly caused by environmental factors such as air pollution and allergens. The development of resistance to existing therapies and increasing air pollution and exposure to allergens have made asthma a major health problem. The molecular mechanisms underlying an asthmatic reaction in the lung caused by airborne allergens are not well understood, but recent experimental evidence exists indicating that this reaction is mainly driven by type 2 innate lymphoid cells (ILC2) and CD4+ type 2 T helper cells (Th2). These cells support allergic reactions by producing cytokines such as IL4 or IL5 leading to eosinophilia. It has been shown that GFI1, a zinc finger transcription factor involved in hematopoiesis and inflammation, regulates many cells involved in the Th2 type immune response including ILC2 or Th2 T cells. Although Gfi1 deficient mice lack functional ILC2 and Th2 T cells and fail to produce IL5, they still show a robust response to allergens with features such as increased expression of mucus-associated genes and lung fibrosis. In particular, GFI1 KO mice still have an accumulation of  CD11c+SiglecFhigh eosinophils to the lungs in response to allergen. In addition, Gfi1 KO mice have a higher expression of Il13 mRNA in the lungs after allergen stimulation and Gfi1 null CD11c+SiglecFhigh eosinophils express Il13ra1. These data suggests that GFI1 KO mice can adapt their response to the allergen by using a different mechanism than WT mice. These findings may have implications for the currently used allergy therapies using anti-IL5 antibodies and may explain the occurrence of resistance towards this treatment.    

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