The DOI matches its Crossref record; 226 of the 231 references it cites were found in a registry or an index.
Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis
Open accessAbstract
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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“Activation of NRF2 by AHR ligands such as coal tar abolished IL-4/IL-13–mediated inhibition of epidermal barrier proteins such as FLG and LOR (42, 56).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [42]
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“AhR ligands can also signal via Nuclear factor erythroid 2-related factor 2 (Nrf2)48–51, a pleiotropic transcription factor involved in redox homeostasis, metabolism, and immune modulation52.”
From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [48]
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Zhang, J., Sun, L., Li, W., Wang, Y., Li, X., & Liu, Y. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108844 · Cited by 15
RetractedDiagnostic features of atopic dermatitis
Hanifin, J. M., & Rajka, G. (1980) · Acta Dermato-Venereologica · doi:10.2340/00015555924447 · Cited by 5,086
Palmer, C. N. A., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., Goudie, D. R., Sandilands, A., Campbell, L. E., Smith, F. J. D., et al. (2006) · Nature Genetics · doi:10.1038/ng1767 · Cited by 2,978
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis
Simpson, E. L., Bieber, T., Guttman-Yassky, E., Beck, L. A., Blauvelt, A., Cork, M. J., Silverberg, J. I., Deleuran, M., Kataoka, Y., Lacour, J.-P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1610020 · Cited by 2,110
The skin: an indispensable barrier
Proksch, E., Brandner, J. M., & Jensen, J. (2008) · Experimental Dermatology · doi:10.1111/j.1600-0625.2008.00786.x · Cited by 2,054
Secukinumab in plaque psoriasis—results of two phase 3 trials
Langley, R. G., Elewski, B. E., Lebwohl, M., Reich, K., Griffiths, C. E. M., Papp, K., Puig, L., Nakagawa, H., Spelman, L., Sigurgeirsson, B., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1314258 · Cited by 1,997
The IL-17 Family of Cytokines in Health and Disease
McGeachy, M. J., Cua, D. J., & Gaffen, S. L. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.021 · Cited by 1,443
IL-22 Increases the Innate Immunity of Tissues
Wolk, K., Kunz, S., Witte, E., Friedrich, M., Asadullah, K., & Sabat, R. (2004) · Immunity · doi:10.1016/j.immuni.2004.07.007 · Cited by 1,406
Cytokine modulation of atopic dermatitis filaggrin skin expression
Howell, M. D., Kim, B. E., Gao, P., Grant, A. V., Boguniewicz, M., DeBenedetto, A., Schneider, L., Beck, L. A., Barnes, K. C., & Leung, D. Y. M. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.04.031 · Cited by 1,084
Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris
Smith, F. J. D., Irvine, A. D., Terron-Kwiatkowski, A., Sandilands, A., Campbell, L., Zhao, Y., Liao, H., Evans, A. T., Goudie, D. R., Lewis‐Jones, S., et al. (2006) · Nature Genetics · doi:10.1038/ng1743 · Cited by 1,026
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5 of the 231 references couldn’t be matched to a known paper.
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Fang, Z., Pan, T., Li, L., Wang, H., Zhu, J., Zhang, H., Zhao, J., Chen, W., & Lu, W. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2044723 · Cited by 273
Fang, Z., Li, L., Zhang, H., Zhao, J., Lu, W., & Chen, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.720393 · Cited by 200
Particulate matter causes skin barrier dysfunction.
Kim, B. E., Kim, J., Goleva, E., Berdyshev, E., Lee, J., Vang, K. A., Lee, U. H., Han, S., Leung, S., Hall, C. F., et al. (2021) · JCI insight · doi:10.1172/jci.insight.145185 · Cited by 173
“barrier proteins such as FLG and LOR (42, 56).”
BackgroundInfluentialFurue, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9113741 · Cited by 161
Self-citationmiR-223: An Effective Regulator of Immune Cell Differentiation and Inflammation
Jiao, P., Wang, X.-P., Luoreng, Z.-M., Yang, J., Jia, L., Ma, Y., & Wei, D.-W. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.59876 · Cited by 151
Metadata
- 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)
- 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
- 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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