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NRF2 Augments Epidermal Antioxidant Defenses and Promotes Atopy.

Authors :
Ogawa T
Ishitsuka Y
Nakamura Y
Kubota N
Saito A
Fujisawa Y
Watanabe R
Okiyama N
Suga Y
Roop DR
Fujimoto M
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 Aug 15; Vol. 205 (4), pp. 907-914. Date of Electronic Publication: 2020 Jul 20.
Publication Year :
2020

Abstract

Atopic dermatitis is a chronic form of allergic contact dermatitis that is closely associated with a compromised epidermal barrier. Immunogenicity of a given electrophilic hapten after penetration of this barrier depends directly on biochemical reactions in the thiol-rich layer in the stratum granulosum. In response to electrophilic hapten, NF-erythroid 2-related factor 2 (NRF2) in keratinocytes efficiently induces the production of antioxidants. In this study, we show that the immunogenicity of a given hapten depends directly on the extent to which it induces antioxidant host defenses within the epidermal tissue. We found that allergic contact dermatitis did not develop in NRF2-deficient mice because of compromise of the epidermal innate immune responses that upregulate IL-1α. We also analyzed epidermal NRF2 in association with congenital disorders with features similar to atopic dermatitis in humans. Epidermal samples from patients with Netherton syndrome and peeling skin syndrome exhibited elevated levels of NRF2 and also elevated levels of its downstream target, small proline-rich protein 2. Taken together, these results suggest that the thiol-mediated biochemical responses in the stratum granulosum provide a critical link between defective epidermal barrier function and the development of atopy. Likewise, our results suggested that NRF2 may have a profound impact on the generation of cutaneous immunological memory.<br /> (Copyright © 2020 by The American Association of Immunologists, Inc.)

Details

Language :
English
ISSN :
1550-6606
Volume :
205
Issue :
4
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
32690656
Full Text :
https://doi.org/10.4049/jimmunol.2000274