BACKGROUND: We have successfully generated an IgE-associated (extrinsic/allergic) mouse model of atopic dermatitis in K14-IL-4-Tg/CByB6 mice. The newly described subset of non-IgE-associated (intrinsic/non-allergic) atopic dermatitis in human patients raises the question on the role of IgE in the pathogenesis. OBJECTIVE: The aim of this study was to develop a non-IgE-associated atopic dermatitis model in K14-IL-4-Tg/SKH1 mice. METHODS: K14-IL-4-Tg/CByB6 mice were crossed with SKH1 mice to produce K14-IL-4-Tg/SKH1 mice. Phenotypes of clinical and histological, cytokine expression in the skin lesions, and total serum IgE in K14-IL-4-Tg/CByB6 and K14-IL-4-Tg/SKH1 mice were compared. The CD40 and CD40L on T and B cells were also studied to differentiate their roles in IgE production. RESULTS: K14-IL-4-Tg/SKH1mice had a normal total serum IgE level and manifested a chronic inflammatory skin phenotype identical to that of K14-IL-4-Tg/CByB6 IgE-mediated mice in clinical morphology, histology, infiltration of mononuclear cells/eosinophils/mast cells, mast cell degranulation, and up-regulation of chronic lesional cytokine mRNA expression of IL-1 beta, IL-3, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-gamma, TNF-alpha, and TNF-beta. We also found that the inability of CD4(+) T cells of the K14-IL-4-Tg/SKH1mice to up-regulate CD40L expression upon stimulation might account for their inability to up-regulate the IgE level. B cell abnormality was ruled out as CD19(+) B cells of K14-IL-4-Tg/SKH1 mice synthesized the same amount of IgE in vitro compared with K14-IL-4-Tg/CByB6 mice in the presence of IL-4 and soluble CD40L. Our studies further suggested that the defect of early growth response-1 in T cells might be responsible for the impaired CD40L up-regulation in K14-IL-4-Tg/SKH1 mice. CONCLUSION: K14-IL-4-Tg/SKH1 mice developed skin inflammation that resembled human intrinsic atopic dermatitis. Therefore, this model may be suitable to study the pathogenesis of intrinsic atopic dermatitis.
BACKGROUND: We have successfully generated an IgE-associated (extrinsic/allergic) mouse model of atopic dermatitis in K14-IL-4-Tg/CByB6 mice. The newly described subset of non-IgE-associated (intrinsic/non-allergic) atopic dermatitis in humanpatients raises the question on the role of IgE in the pathogenesis. OBJECTIVE: The aim of this study was to develop a non-IgE-associated atopic dermatitis model in K14-IL-4-Tg/SKH1 mice. METHODS: K14-IL-4-Tg/CByB6 mice were crossed with SKH1 mice to produce K14-IL-4-Tg/SKH1 mice. Phenotypes of clinical and histological, cytokine expression in the skin lesions, and total serum IgE in K14-IL-4-Tg/CByB6 and K14-IL-4-Tg/SKH1 mice were compared. The CD40 and CD40L on T and B cells were also studied to differentiate their roles in IgE production. RESULTS: K14-IL-4-Tg/SKH1mice had a normal total serum IgE level and manifested a chronic inflammatory skin phenotype identical to that of K14-IL-4-Tg/CByB6 IgE-mediated mice in clinical morphology, histology, infiltration of mononuclear cells/eosinophils/mast cells, mast cell degranulation, and up-regulation of chronic lesional cytokine mRNA expression of IL-1 beta, IL-3, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-gamma, TNF-alpha, and TNF-beta. We also found that the inability of CD4(+) T cells of the K14-IL-4-Tg/SKH1mice to up-regulate CD40L expression upon stimulation might account for their inability to up-regulate the IgE level. B cell abnormality was ruled out as CD19(+) B cells of K14-IL-4-Tg/SKH1 mice synthesized the same amount of IgE in vitro compared with K14-IL-4-Tg/CByB6 mice in the presence of IL-4 and soluble CD40L. Our studies further suggested that the defect of early growth response-1 in T cells might be responsible for the impaired CD40L up-regulation in K14-IL-4-Tg/SKH1 mice. CONCLUSION: K14-IL-4-Tg/SKH1 mice developed skin inflammation that resembled human intrinsic atopic dermatitis. Therefore, this model may be suitable to study the pathogenesis of intrinsic atopic dermatitis.
Authors: Svetlana V Guryanova; Ekaterina I Finkina; Daria N Melnikova; Ivan V Bogdanov; Barbara Bohle; Tatiana V Ovchinnikova Journal: Front Mol Biosci Date: 2022-06-16
Authors: Padraic G Fallon; Takashi Sasaki; Aileen Sandilands; Linda E Campbell; Sean P Saunders; Niamh E Mangan; John J Callanan; Hiroshi Kawasaki; Aiko Shiohama; Akiharu Kubo; John P Sundberg; Richard B Presland; Philip Fleckman; Nobuyoshi Shimizu; Jun Kudoh; Alan D Irvine; Masayuki Amagai; W H Irwin McLean Journal: Nat Genet Date: 2009-04-06 Impact factor: 38.330