Cited by 424Dermatology and Skin DiseasesPsoriasis: Treatment and PathogenesisContact Dermatitis and Allergies

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Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis

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Furue, Masutaka·2020·International Journal of Molecular Sciences

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Abstract

Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD.

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Authors: Furue, M.
Affiliations: Kyushu University (JP)
Corresponding author: Furue, Masutaka
ORCID: Furue, Masutaka
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2020-07-29
Volume: 21
Issue: 15
Pages: 5382
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms21155382
PMC: PMC7432778
OpenAlex: W3046068546
Cited by: 419
References: 231
Citations by year: 2026: 83 · 2025: 82 · 2024: 81 · 2023: 74 · 2022: 64 · 2021: 32 · 2020: 2
FWCI: 7.19
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Ministry of Health, Labour and Welfare (H30-Shokuhin-Shitei-005)
Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (C, FAG0K08692)
Topics: Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Keywords: atopic dermatitis, filaggrin, loricrin, involucrin, skin barrier dysfunction, IL-4, IL-13, IL-17A, IL-22, aryl hydrocarbon receptor, Nrf2, STAT6, STAT3, oxidative stress, coal tar, tapinarof, AhR agonists
MeSH terms: Filaggrin Proteins, Interleukin-22, Antioxidants, Coal Tar, Dermatitis, Atopic, Gene Expression Regulation, Humans, Interleukins, Membrane Proteins, S100 Proteins, Protein Precursors, Resorcinols, Skin, Stilbenes, Tars, Signal Transduction, Interleukin-4, Receptors, Aryl Hydrocarbon, Oxidative Stress, Interleukin-13, Interleukin-17, STAT3 Transcription Factor, STAT6 Transcription Factor, NF-E2-Related Factor 2, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins

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Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis

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