NRF2 Augments Epidermal Antioxidant Defenses and Promotes Atopy.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Tatsuya OgawaManabu Fujimoto

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 ...Continue Reading

References

Jun 1, 1994·The Journal of Investigative Dermatology·G SenaldiG E Grau
Mar 2, 1999·The Journal of Experimental Medicine·J KehrenJ F Nicolas
May 7, 1999·Experimental & Molecular Medicine·Z Nemes, P M Steinert
Sep 18, 2002·The Journal of Biological Chemistry·Hiromi SasakiShiro Bannai
Oct 1, 2003·Nature Genetics·Nobunao WakabayashiMasayuki Yamamoto
Apr 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hideki WatanabeOlivier Gaide
Sep 16, 2008·Immunity·Anne GoubierDominique Kaiserlian
Nov 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chris PickardPeter S Friedmann
May 19, 2010·Genes & Development·Matthias SchäferSabine Werner
Feb 26, 2011·Nature Reviews. Immunology·Polly Matzinger, Tirumalai Kamala
Oct 14, 2011·The New England Journal of Medicine·Alan D IrvineDonald Y M Leung
Jan 14, 2012·Nature Reviews. Immunology·Daniel H KaplanAnthony A Gaspari
Apr 3, 2012·The Journal of Allergy and Clinical Immunology·Gideon Lack
Apr 24, 2012·The Journal of Clinical Investigation·Mercedes Gomez de AgüeroBertrand Dubois
Aug 30, 2014·Molecular Biology and Evolution·Bettina StrasserLeopold Eckhart
Oct 6, 2014·The Journal of Allergy and Clinical Immunology·Liat Samuelov, Eli Sprecher
Mar 20, 2015·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Mar 31, 2015·International Immunology·Takeshi Matsui, Masayuki Amagai
May 12, 2016·The Journal of Investigative Dermatology·Yosuke IshitsukaDennis R Roop
Nov 22, 2016·The Journal of Clinical Investigation·Trevor J CunninghamShadmehr Demehri
Jun 7, 2017·The Journal of Allergy and Clinical Immunology·Tali CzarnowickiEmma Guttman-Yassky
May 3, 2018·Physiological Reviews·Masayuki YamamotoHozumi Motohashi
Jun 23, 2018·The Journal of Investigative Dermatology·Yosuke Ishitsuka, Dennis R Roop
Jul 18, 2018·Nature Immunology·Greg CrawfordJessica Strid
Nov 11, 2018·The Journal of Allergy and Clinical Immunology·Kilian EyerichNick J Reynolds
Mar 10, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Doumet Georges HelouSaadia Kerdine-Römer

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Citations

Sep 29, 2020·Clinical, Cosmetic and Investigational Dermatology·Tatsuya OgawaManabu Fujimoto
Aug 23, 2020·Antioxidants·Yosuke IshitsukaDennis Roop
Dec 4, 2020·Tissue Barriers·Yosuke IshitsukaTatsuya Ogawa
Apr 4, 2021·Cancers·Yosuke IshitsukaManabu Fujimoto

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