The development of atopic dermatitis is independent of Immunoglobulin E up-regulation in the K14-IL-4 SKH1 transgenic mouse model
Article first published online: 13 APR 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 38, Issue 8, pages 1367–1380, August 2008
How to Cite
Chen, L., Overbergh, L., Mathieu, C. and Chan, L. S. (2008), The development of atopic dermatitis is independent of Immunoglobulin E up-regulation in the K14-IL-4 SKH1 transgenic mouse model. Clinical & Experimental Allergy, 38: 1367–1380. doi: 10.1111/j.1365-2222.2008.02987.x
- Issue published online: 18 JUL 2008
- Article first published online: 13 APR 2008
- Submitted 2 November 2007; revised 15 January 2008; accepted 21 February 2008
- animal model;
- 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 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-1β, IL-3, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, and TNF-β. 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.