Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model
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<sub>3</sub>-analog (MC903) was used t...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/6311 |
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| author | Sofie Svanberg Zhiqiang Li Pontus Öhlund Ananya Roy Magnus Åbrink |
| author_facet | Sofie Svanberg Zhiqiang Li Pontus Öhlund Ananya Roy Magnus Åbrink |
| author_sort | Sofie Svanberg |
| collection | DOAJ |
| description | 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<sub>3</sub>-analog (MC903) was used to induce clinical AD-like symptoms in c-kit-dependent MC-deficient Wsh<sup>−/−</sup> and the MC protease-deficient mMCP-4<sup>−/−</sup>, mMCP-6<sup>−/−</sup>, and CPA3<sup>−/−</sup> 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<sup>−/−</sup> 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<sup>−/−</sup> 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. |
| first_indexed | 2024-03-10T16:40:41Z |
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| id | doaj.art-4d526e3a32b74ddcb99a7bb717cef5f8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:40:41Z |
| publishDate | 2020-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4d526e3a32b74ddcb99a7bb717cef5f82023-11-20T12:01:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117631110.3390/ijms21176311Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse ModelSofie Svanberg0Zhiqiang Li1Pontus Öhlund2Ananya Roy3Magnus Åbrink4Evidensia Djurkliniken Öjebyn, Öjagatan 81, 94331 Öjebyn, SwedenSection of Immunology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007 Uppsala, SwedenSection of Virology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, SwedenSection of Immunology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007 Uppsala, SwedenAtopic 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<sub>3</sub>-analog (MC903) was used to induce clinical AD-like symptoms in c-kit-dependent MC-deficient Wsh<sup>−/−</sup> and the MC protease-deficient mMCP-4<sup>−/−</sup>, mMCP-6<sup>−/−</sup>, and CPA3<sup>−/−</sup> 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<sup>−/−</sup> 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<sup>−/−</sup> 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.https://www.mdpi.com/1422-0067/21/17/6311mouse mast cell chymase 4 (mMCP-4), knockoutMC903atopic dermatitisIL-33thymic stromal lymphopoietin |
| spellingShingle | Sofie Svanberg Zhiqiang Li Pontus Öhlund Ananya Roy Magnus Åbrink 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 mouse mast cell chymase 4 (mMCP-4), knockout MC903 atopic dermatitis IL-33 thymic stromal lymphopoietin |
| title | Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model |
| title_full | Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model |
| title_fullStr | Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model |
| title_full_unstemmed | Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model |
| title_short | Mast Cells Limit Ear Swelling Independently of the Chymase Mouse Mast Cell Protease 4 in an MC903-Induced Atopic Dermatitis-Like Mouse Model |
| title_sort | mast cells limit ear swelling independently of the chymase mouse mast cell protease 4 in an mc903 induced atopic dermatitis like mouse model |
| topic | mouse mast cell chymase 4 (mMCP-4), knockout MC903 atopic dermatitis IL-33 thymic stromal lymphopoietin |
| url | https://www.mdpi.com/1422-0067/21/17/6311 |
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