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Mast cell dependent IL-33/ST2 signaling is protective against the development of airway hyperresponsiveness in a house dust mite mouse model of asthma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden . (Hematologi)
2018 (English)In: American Journal of Physiology - Lung cellular and Molecular Physiology, ISSN 1040-0605, E-ISSN 1522-1504, Vol. 314, no 3, p. L484-L492Article in journal (Refereed) Published
Abstract [en]

Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated to the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM) induced asthma. Mast cell deficient C57BL/6-KitW-sh (Wsh) mice engrafted with either wild-type (Wsh+MC-WT) or ST2 deficient bone marrow derived mast cells (Wsh+MC-ST2KO) were exposed to HDM delivered intranasally. An exacerbated development of AHR in response to HDM was seen in Wsh+MC-ST2KO compared to Wsh+MC-WT mice. The contribution of this IL-33/ST2-dependent mast cell response to AHR seems to reside within the smaller airways in the peripheral parts of the lung, as suggested by the isolated yet marked effect on tissue resistance. Considering the absence of a parallel increase in cellular inflammation in BALF and lung, the aggravated AHR in Wsh+MC-ST2KO mice, seems to be independent of cellular inflammation. We observed an association between the elevated AHR and reduced PGE2 levels in bronchoalveolar lavage fluid. Due to the protective properties of PGE2 in airway responses, it is conceivable that IL-33/ST2-dependent mast cell induction of PGE2 could be responsible for the dampening effect on AHR. In conclusion, we reveal that IL-33/ST2-dependent mast cell responses can have a protective, rather than causative role in the development of AHR.

Place, publisher, year, edition, pages
2018. Vol. 314, no 3, p. L484-L492
Keywords [en]
HDM mouse model, IL-33, ST2, airway hyperresponsiveness (AHR), mast cells
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-343006DOI: 10.1152/ajplung.00270.2017ISI: 000428403800014PubMedID: 29146574OAI: oai:DiVA.org:uu-343006DiVA, id: diva2:1185442
Funder
Swedish Research CouncilSwedish Heart Lung FoundationThe Karolinska Institutet's Research FoundationAvailable from: 2018-02-24 Created: 2018-02-24 Last updated: 2018-07-19Bibliographically approved

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Nilsson, G P

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