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Cited by 21Dermatology and Skin DiseasesIL-33, ST2, and ILC PathwaysPsoriasis: Treatment and Pathogenesis

Regulatory mechanism of the IL-33-IL-37 axis via aryl hydrocarbon receptor in atopic dermatitis and psoriasis

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Tsuji, Gaku, Yamamura, Kazuhiko, Kawamura, Koji, Kido-Nakahara, Makiko, Ito, Takamichi, Nakahara, Takeshi·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms241914633PMC PMC10572928
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Abstract

Interleukin (IL)-33 and IL-37 have been identified as novel cytokines involved in various inflammatory diseases. However, their specific roles remain largely unknown. Recent studies have shown that IL-33, which triggers inflammation, and IL-37, which suppresses it, cooperatively regulate the balance between inflammation and anti-inflammation. IL-33 and IL-37 are also deeply involved in the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Furthermore, a signaling pathway by which aryl hydrocarbon receptor (AHR), a receptor for dioxins, regulates the expression of IL-33 and IL-37 has been revealed. Here, we outline recent findings on the mechanisms regulating IL-33 and IL-37 expression in AD and psoriasis. IL-33 expression is partially dependent on mitogen-activated protein kinase (MAPK) activation, and IL-37 has a role in suppressing MAPK in human keratinocytes. Furthermore, IL-33 downregulates skin barrier function proteins including filaggrin and loricrin, thereby downregulating the expression of IL-37, which colocalizes with these proteins. This leads to an imbalance of the IL-33–IL-37 axis, involving increased IL-33 and decreased IL-37, which may be associated with the pathogenesis of AD and psoriasis. Therefore, AHR-mediated regulation of the IL-33–IL-37 axis may lead to new therapeutic strategies for the treatment of AD and psoriasis.

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  • Coal tar, tapiranof, as well as certain flavonoids, reduce oxidative stress by suppressing pro-inflammatory cytokines and stimulating the restoration of the expression of epidermal barrier proteins.

    “Coal tar, tapiranof, as well as certain flavonoids, reduce oxidative stress by suppressing pro-inflammatory cytokines and stimulating the restoration of the expression of epidermal barrier proteins.73”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [73]

    Section 6 reports that tapinarof suppresses IL-33 and increases the barrier proteins filaggrin and loricrin in human keratinocytes; it also reports that the flavonoids luteolin and apigenin inhibit IL-33 production. The References identify a study of coal-tar-induced skin-barrier repair in atopic dermatitis. The paper does not establish that all three groups reduce oxidative stress by suppressing cytokines and restoring barrier-protein expression; its antioxidant statement concerns certain AHR ligands generally. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Activation of AhRs by different ligands can lead to the stimulation or suppression of different genes, causing a wide variety of biological responses.

    “The activation of AhRs by different ligands can lead to the stimulation or suppression of different genes, causing a wide variety of biological responses.73”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [73]

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Cited by

Sorted by citations

Authors
Tsuji, G., Yamamura, K., Kawamura, K., Kido-Nakahara, M., Ito, T., & Nakahara, T.
Affiliations
  • Kyushu University (JP)
  • Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Corresponding author
Tsuji, Gaku
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-09-27
Volume
24
Issue
19
Pages
14633
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms241914633
PMC
PMC10572928
OpenAlex
W4387100058
Cited by
21
References
7
Citations by year
2026: 6 · 2025: 4 · 2024: 10 · 2023: 1
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Ministry of Health, Labour and Welfare of Japan (H30-Shokuhin-Shitei-005)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
IL-33, IL-37, aryl hydrocarbon receptor, atopic dermatitis, psoriasis, MAPK signaling, keratinocytes, skin barrier function, filaggrin, loricrin, inflammatory skin diseases, cytokine regulation
MeSH terms
Interleukin-33, Dermatitis, Atopic, Humans, Inflammation, Interleukin-1, Psoriasis, Skin, Keratinocytes, Receptors, Aryl Hydrocarbon

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