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Abstract
Cellular, Molecular, and Pharmacological Characterization of a House Dust Mites (HDM)-Induced Murine Model of Dermatitis
Nancy Crosbie, Jacqueline Loud*, Victoria E. Scott, Viktor TodoroviÄ?, Ramkrishna Sadhukhan, Heath A. McDonald, Danyal Butt, Samantha Ciura, Stephanie E. Paulsboe, Gricelda Simler, Elizabeth Asque, Laura Wasserman, Zhi Su, Gunarso Nguyen, Samuel Karsen, Joseph B. Wetter, Anastasia E. Marinopoulos, Stacy H. Ryu, Xin Chen, Kathleen M. Smith, Sheila Cummings, Zachary K. Goldsmith and Samrawit Aforki
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