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Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation

Waern, Ida and Lundequist, Anders and Pejler, Gunnar and Wernersson, Sara (2013). Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation. Mucosal Immunology. 6:5, 911-920
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Official URL: http://dx.doi.org/ 10.1038/mi.2012.129

Abstract

Mast cells (MCs) are major effector cells contributing to allergic conditions. When activated, they can release large amounts of active proteases, including chymase from their secretory granules. Here we assessed the role of the chymase mouse mast cell protease 4 (mMCP-4) in allergic airway inflammation induced by house-dust mite (HDM) extract. mMCP-4(-/-) mice demonstrated elevated airway reactivity and eosinophilia compared with wild-type (WT) animals, suggesting a protective role for mMCP-4 during the late inflammatory phase of the disease. However, mMCP-4 also contributed to the sensitization phase, as indicated by higher levels of serum immunoglobulin E in mMCP-4(-/-) vs. WT mice and higher levels of cytokines secreted by HDM-restimulated mMCP-4(-/-) vs. WT splenocytes. In line with a contribution of mMCP-4 in the early stages of disease, HDM extract directly induced chymase secretion from MCs. The elevated airway and inflammatory responses of mMCP-4(-/-) mice were associated with a profound increase in the levels of interleukin (IL)-33 in the lung tissue. Moreover, WT MCs degraded IL-33 more efficiently than did MCs lacking mMCP-4. Together, our findings identify a protective role of a MC chymase in a physiologically relevant model for airway inflammation and suggest that chymase-mediated regulation of IL-33 can account for this protective function.

Authors/Creators:Waern, Ida and Lundequist, Anders and Pejler, Gunnar and Wernersson, Sara
Title:Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation
Series/Journal:Mucosal Immunology (1933-0219)
Year of publishing :2013
Volume:6
Number:5
Page range:911-920
Number of Pages:10
Publisher:Nature Publishing Group
ISSN:1933-0219
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Accepted version
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X38 Human medicine, health, and safety
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Immunology in the medical area
Keywords:Mast cells, Airway inflamation
URN:NBN:urn:nbn:se:slu:epsilon-e-1657
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-1657
Additional ID:
Type of IDID
Web of Science (WoS)000323331800005
DOI10.1038/mi.2012.129
ID Code:10841
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:10 Oct 2013 12:47
Metadata Last Modified:01 Apr 2015 07:18

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