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.

Keywords

mouse mast cell chymase 4 (mMCP-4); knockout; MC903; atopic dermatitis; IL-33; thymic stromal lymphopoietin

Published in

International Journal of Molecular Sciences
2020, volume: 21, number: 17, article number: 6311
Publisher: MDPI

Authors' information