1. ¹Dermatology and Medical (Metabolism) Services, Veterans Affairs Medical Center, and Departments of Dermatology & Medicine, University of California, San Francisco, California, USA
2. ²Dalian Skin Disease Hospital, Dalian, PR China
3. ³Department of Dermatology, Yonsei University School of Medicine, Seoul, Korea
4. ⁴Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA

Correspondence: Dr Peter M. Elias, Dermatology Service (190), VA Medical Center, 4150 Clement Street, San Francisco, California 94121, USA. E-mail: eliasp@derm.ucsf.edu

⁵These authors contributed equally to this work, and shall be considered as co-first authors

Received 5 March 2007; Revised 16 May 2007; Accepted 24 May 2007; Published online 2 August 2007.

Abstract

Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureas colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9–10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.