Abstract

Cellular, Molecular, and Pharmacological Characterization of a House Dust Mites (HDM)-Induced Murine Model of Dermatitis

Zhi Su

Background: House Dust Mites (HDM), common allergens that can induce Atopic Dermatitis (AD), are widely employed to generate mouse models of AD. In the current study, we compared the AD-like phenotypes between two mouse strains, NC/Nga, and BALB/c, in response to HDM, and performed cellular, molecular, and pharmacological characterization of HDM-induced dermatitis in NC/Nga mice.

Methods: In-life endpoints (skin clinical scores, ear thickness, Transepithelial Water Loss (TEWL), scratching bouts) and terminal endpoints (histopathology, total serum IgE and tissue cytokines) were measured. Further phenotyping of NC/Nga was performed by flow cytometry, gene expression analysis, and pharmacology.

Results: HDM applications resulted in a more robust AD-like dermatitis in NC/Nga than BALB/c mice as evidenced by greater changes in in-life endpoints (clinical scores, ear thickness, scratching bouts, and TEWL), histological markers (overall inflammation, acanthosis, and parakeratosis), and tissue inflammatory cytokines although serum total IgE level is higher in BALB/c than NC/Nga mice. Further flow cytometry analysis of skin immune cells in HDM-treated NC/Nga mice showed increased production of IL-4, IL-13, IL-17A and IFNγ, which was mainly from CD3- cells other than CD3+ cells. The immune/inflammatory responses in NC/Nga mice are supported by gene expression analysis, where multiple pathways are similar to human AD lesional skin. Treatment with JAK1 inhibitor or IL-4R antibody attenuated multiple AD-relevant endpoints in NC/Nga mice.

Conclusion: These data confirm NC/Nga mice are predisposed to HDM-induced dermatitis compared to BALB/c, and their immune profile is complex and shares several relevant pathways/pharmacological mechanisms with human AD.

Published Date: 2026-01-11; Received Date: 2024-11-08