Research article - Peer-reviewed, 2020
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; Li, Zhiqiang; Ohlund, Pontus; Roy, Ananya; Abrink, MagnusAbstract
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.Keywords
mouse mast cell chymase 4 (mMCP-4); knockout; MC903; atopic dermatitis; IL-33; thymic stromal lymphopoietinPublished in
International Journal of Molecular Sciences2020, volume: 21, number: 17, article number: 6311
Publisher: MDPI
Authors' information
Svanberg, Sofie
Evidensia Djurkliniken Ojebyn
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Guizhou Medical University
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Roy, Ananya
Uppsala University
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
UKÄ Subject classification
Biochemistry and Molecular Biology
Publication Identifiers
DOI: https://doi.org/10.3390/ijms21176311
URI (permanent link to this page)
https://res.slu.se/id/publ/108157