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

Sensitization via healthy skin programmes: Th2 responses in individuals with atopic dermatitis
Sensitization via healthy skin programmes: Th2 responses in individuals with atopic dermatitis
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.
0022-202X
2372-2380
Newell, Louise
ce1ca744-215b-4307-8b4b-ff6fcfdd5157
Polak, Marta E.
e0ac5e1a-7074-4776-ba23-490bd4da612d
Perera, Jay
edcdc399-971c-44d1-bd5f-a6135c298292
Owen, Charlotte
8355311c-59f6-474a-80f0-17e88b5a4083
Boyd, Peter
6013fab6-52a0-498d-a2e5-9cf9eb306b3a
Pickard, Christopher
4d8b8c85-8118-4a54-b737-360344ab6e40
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Healy, Eugene
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Ardern-Jones, Michael R.
7ac43c24-94ab-4d19-ba69-afaa546bec90
Newell, Louise
ce1ca744-215b-4307-8b4b-ff6fcfdd5157
Polak, Marta E.
e0ac5e1a-7074-4776-ba23-490bd4da612d
Perera, Jay
edcdc399-971c-44d1-bd5f-a6135c298292
Owen, Charlotte
8355311c-59f6-474a-80f0-17e88b5a4083
Boyd, Peter
6013fab6-52a0-498d-a2e5-9cf9eb306b3a
Pickard, Christopher
4d8b8c85-8118-4a54-b737-360344ab6e40
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Healy, Eugene
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Ardern-Jones, Michael R.
7ac43c24-94ab-4d19-ba69-afaa546bec90

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)

Record type: Article

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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More information

e-pub ahead of print date: 9 May 2013
Published date: October 2013
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 350832
URI: http://eprints.soton.ac.uk/id/eprint/350832
ISSN: 0022-202X
PURE UUID: 28579217-e606-4f71-b387-fc8db3c43d68
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Michael R. Ardern-Jones: ORCID iD orcid.org/0000-0003-1466-2016

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Date deposited: 08 Apr 2013 13:25
Last modified: 23 Jul 2022 01:57

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Contributors

Author: Louise Newell
Author: Marta E. Polak
Author: Jay Perera
Author: Charlotte Owen
Author: Peter Boyd
Author: Christopher Pickard
Author: Peter Howarth
Author: Eugene Healy
Author: Peter S. Friedmann

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