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<p>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. In-life endpoints included skin clinical scores, ear thickness, transepidermal water loss (TEWL), and scratching bouts. Terminal endpoints included histopathology, total serum IgE and tissue cytokines. Further phenotyping of NC/Nga was performed by flow cytometry, gene expression analysis, and pharmacology. 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. 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<sup>−</sup> 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 anti-IL-4Rα antibody attenuated multiple AD-relevant endpoints in NC/Nga mice. These data confirm NC/Nga mice are predisposed to HDM-induced dermatitis compared to BALB/c, and reveal a complex immune profile that shares several relevant pathways and pharmacological mechanisms with human AD.</p>

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Translational characterization of a house dust mite-induced murine model of dermatitis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月10日

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  • Zhi Su,
  • Samrawit Aforki,
  • Zachary K. Goldsmith,
  • Sheila Cummings,
  • Kathleen M. Smith,
  • Xin Chen,
  • Stacy H. Ryu,
  • Anastasia E. Marinopoulos,
  • Joseph B. Wetter,
  • Samuel Karsen,
  • Nancy Crosbie,
  • Laura Wasserman,
  • Elizabeth Asque,
  • Gricelda Simler,
  • Stephanie E. Paulsboe,
  • Samantha Ciura,
  • Danyal Butt,
  • Heath A. McDonald,
  • Ramkrishna Sadhukhan,
  • Viktor Todorović,
  • Victoria E. Scott,
  • Jacqueline Loud

摘要

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. In-life endpoints included skin clinical scores, ear thickness, transepidermal water loss (TEWL), and scratching bouts. Terminal endpoints included histopathology, total serum IgE and tissue cytokines. Further phenotyping of NC/Nga was performed by flow cytometry, gene expression analysis, and pharmacology. 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. 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. 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 anti-IL-4Rα antibody attenuated multiple AD-relevant endpoints in NC/Nga mice. These data confirm NC/Nga mice are predisposed to HDM-induced dermatitis compared to BALB/c, and reveal a complex immune profile that shares several relevant pathways and pharmacological mechanisms with human AD.