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Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model

Svanberg, Sofie and Li, Zhiqiang and Öhlund, Pontus and Roy, Ananya and Åbrink, Magnus (2020). Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model. International Journal of Molecular Sciences. 21 , 6311
[Research article]

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Abstract

Atopic dermatitis (AD) is a complex, often lifelong allergic disease with severe pruritus affecting around 10% of both humans and dogs. To investigate the role of mast cells (MCs) and MC-specific proteases on the immunopathogenesis of AD, a vitamin D-3-analog (MC903) was used to induce clinical AD-like symptoms in c-kit-dependent MC-deficient Wsh(-/-)and the MC protease-deficient mMCP-4(-/-), mMCP-6(-/-), and CPA3(-/-)mouse strains. MC903-treatment on the ear lobe increased clinical scores and ear-thickening, along with increased MC and granulocyte infiltration and activity, as well as increased levels of interleukin 33 (IL-33) locally and thymic stromal lymphopoietin (TSLP) both locally and systemically. The MC-deficient Wsh(-/-)mice showed significantly increased clinical score and ear thickening albeit having lower ear tissue levels of IL-33 and TSLP as well as lower serum levels of TSLP as compared to the WT mice. In contrast, although having significantly increased IL-33 ear tissue levels the chymase-deficient mMCP-4(-/-)mice showed similar clinical score, ear thickening, and TSLP levels in ear tissue and serum as the WT mice, whereas mMCP-6 and CPA3 -deficient mice showed a slightly reduced ear thickening and granulocyte infiltration. Our results suggest that MCs promote and control the level of MC903-induced AD-like inflammation.

Authors/Creators:Svanberg, Sofie and Li, Zhiqiang and Öhlund, Pontus and Roy, Ananya and Åbrink, Magnus
Title:Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model
Series Name/Journal:International Journal of Molecular Sciences
Year of publishing :2020
Volume:21
Article number:6311
Number of Pages:18
Publisher:MDPI
ISSN:1661-6596
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
Keywords:mouse mast cell chymase 4 (mMCP-4), knockout, MC903, atopic dermatitis, IL-33, thymic stromal lymphopoietin
URN:NBN:urn:nbn:se:slu:epsilon-p-108157
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-108157
Additional ID:
Type of IDID
DOI10.3390/ijms21176311
Web of Science (WoS)000571623600001
ID Code:22676
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:01 Mar 2021 08:43
Metadata Last Modified:01 Mar 2021 08:51

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