Sensitization via healthy skin programmes: Th2 responses in individuals with atopic dermatitis

Newell, Louise, Polak, Marta E., Perera, Jay, Owen, Charlotte, Boyd, Peter, Pickard, Christopher, Howarth, Peter, Healy, Eugene, Holloway, John W., Friedmann, Peter S. and Ardern-Jones, Michael R. (2013) Sensitization via healthy skin programmes: Th2 responses in individuals with atopic dermatitis. Journal of Investigative Dermatology, 133 (10), 2372-2380. (doi:10.1038/jid.2013.148). (PMID:23528819)

Abstract

Allergen-specific responses in AD are skewed towards a Th2 profile. However, individuals with AD have been shown to make effective virus-specific Th1 responses raising the possibility that the skin itself contributes to driving the AD Th2 immuno-phenotype. Therefore, to explore the programming of immunological sensitization by the skin, we examined the outcome of sensitization through non-lesional skin of AD and healthy controls. Volunteers, (controls, AD with Filaggrin gene (FLG) mutations (ADFM) and AD without FLG mutations (ADWT)) were sensitized by cutaneous application of 2,4-dinitrochlorobenzene (DNCB), a small, highly lipophilic chemical sensitizer. At the doses tested, DNCB showed equal penetration into skin of all groups. Clinical reactions to DNCB were significantly reduced in AD. Although both controls and AD made systemic DNCB-specific Th1 responses, these were reduced in AD and associated with significantly Th2-skewed DNCB-specific T cell responses. Th2 skewing was seen in both ADFM and ADWT with no difference between these groups. After 3 months DNCB-specific Th2 responses were persistent in AD, and Th1 responses persisted in controls. These data provide evidence that when antigen penetration is not limiting, AD skin has a specific propensity to Th2 programming suggesting the existence of altered skin immune signaling which is AD-specific and independent of FLG status.

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Contributors

Author: John W. Holloway

Author: Michael R. Ardern-Jones

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