{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:12:13Z","timestamp":1790050333445,"version":"4.0.1"},"reference-count":122,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare of Japan","doi-asserted-by":"publisher","award":["H30-Shokuhin-Shitei-005"],"award-info":[{"award-number":["H30-Shokuhin-Shitei-005"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013IL-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\u2013IL-37 axis may lead to new therapeutic strategies for the treatment of AD and psoriasis.<\/jats:p>","DOI":"10.3390\/ijms241914633","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:38:46Z","timestamp":1695800326000},"page":"14633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Regulatory Mechanism of the IL-33\u2013IL-37 Axis via Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis"],"prefix":"10.3390","volume":"24","author":[{"given":"Gaku","family":"Tsuji","sequence":"first","affiliation":[{"name":"Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Kido-Nakahara","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2679-8546","authenticated-orcid":false,"given":"Takamichi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.immuni.2013.11.010","article-title":"The Interleukin-1 Family: Back to the Future","volume":"39","author":"Garlanda","year":"2013","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vasanthakumar, A., and Kallies, A. (2019). Interleukin (IL)-33 and the IL-1 Family of Cytokines-Regulators of Inflammation and Tissue Homeostasis. Cold Spring Harb. Perspect. Biol., 11.","DOI":"10.1101\/cshperspect.a028506"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Conti, P., Pregliasco, F.E., Bellomo, R.G., Gallenga, C.E., Caraffa, A., Kritas, S.K., Lauritano, D., and Ronconi, G. (2021). Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158076"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"752","DOI":"10.3389\/fimmu.2020.00752","article-title":"IL-37 Ameliorating Allergic Inflammation in Atopic Dermatitis Through Regulating Microbiota and AMPK-mTOR Signaling Pathway-Modulated Autophagy Mechanism","volume":"11","author":"Hou","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Borgia, F., Custurone, P., Li Pomi, F., Vaccaro, M., Alessandrello, C., and Gangemi, S. (2022). IL-33 and IL-37: A Possible Axis in Skin and Allergic Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010372"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/all.15072","article-title":"IL-37 Regulates Allergic Inflammation by Counterbalancing Pro-inflammatory IL-1 and IL-33","volume":"77","author":"Lunding","year":"2022","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Furue, M., Hashimoto-Hachiya, A., and Tsuji, G. (2019). Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215424"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.jid.2020.12.013","article-title":"The Enigma of AHR Activation in the Skin: Interplay among Ligands, Metabolism, and Bioavailability","volume":"141","author":"Perdew","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Napolitano, M., Fabbrocini, G., Martora, F., Picone, V., Morelli, P., and Patruno, C. (2021). Role of Aryl Hydrocarbon Receptor Activation in Inflammatory Chronic Skin Diseases. Cells, 10.","DOI":"10.3390\/cells10123559"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cardinali, G., Flori, E., Mastrofrancesco, A., Ottaviani, M., Dell\u2019Anna, M.L., Truglio, M., Vento, A., Zaccarini, M., Zouboulis, C.C., and Picardo, M. (2021). Anti-Inflammatory and Pro-Differentiating Properties of the Aryl Hydrocarbon Receptor Ligands NPD-0614-13 and NPD-0614-24: Potential Therapeutic Benefits in Psoriasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147501"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.immuni.2005.09.015","article-title":"IL-33, an Interleukin-1-like Cytokine that Signals via the IL-1 Receptor-Related Protein ST2 and Induces T Helper Type 2-Associated Cytokines","volume":"23","author":"Schmitz","year":"2005","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1136\/ard.2009.119321","article-title":"The IL1-like Cytokine IL33 and its Receptor ST2 Are Abnormally Expressed in the Affected Skin and Visceral Organs of Patients with Systemic Sclerosis","volume":"69","author":"Manetti","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ajpath.2011.03.010","article-title":"The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation","volume":"179","author":"Byrne","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.imlet.2011.07.005","article-title":"Prostaglandin E(2) Enhances IL-33 Production by Dendritic Cells","volume":"141","author":"Yanagawa","year":"2011","journal-title":"Immunol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ni.2045","article-title":"Innate Lymphoid Cells Mediate Influenza-Induced Airway Hyper-reactivity Independently of Adaptive Immunity","volume":"12","author":"Chang","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.4049\/jimmunol.1201224","article-title":"Inducible IL-33 Expression by Mast Cells Is Regulated by a Calcium-Dependent Pathway","volume":"189","author":"Hsu","year":"2012","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1073\/pnas.0606854104","article-title":"IL-33, the IL-1-like Cytokine Ligand for ST2 Receptor, Is a Chromatin-Associated Nuclear Factor In Vivo","volume":"104","author":"Carriere","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/s41590-021-01011-2","article-title":"Environmental Allergens Trigger Type 2 Inflammation through Ripoptosome Activation","volume":"22","author":"Brusilovsky","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.4049\/jimmunol.1601223","article-title":"Highly Selective Cleavage of Cytokines and Chemokines by the Human Mast Cell Chymase and Neutrophil Cathepsin G","volume":"198","author":"Fu","year":"2017","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1038\/s41467-018-05485-x","article-title":"Chromatin Regulates IL-33 Release and Extracellular Cytokine Activity","volume":"9","author":"Travers","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1046\/j.1432-1327.1999.00615.x","article-title":"Different Promoter Usage and Multiple Transcription Initiation Sites of the Interleukin-1 Receptor-Related Human ST2 Gene in UT-7 and TM12 Cells","volume":"264","author":"Iwahana","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26369","DOI":"10.1074\/jbc.M704916200","article-title":"Soluble ST2 Blocks Interleukin-33 Signaling in Allergic Airway Inflammation","volume":"282","author":"Hayakawa","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nrd2660","article-title":"The IL-33\/ST2 Pathway: Therapeutic Target and Novel Biomarker","volume":"7","author":"Kakkar","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00403-014-1447-9","article-title":"IL-33 is regulated by TNF-\u03b1 in normal and psoriatic skin","volume":"306","author":"Balato","year":"2014","journal-title":"Arch. Dermatol. Res."},{"key":"ref_25","first-page":"428","article-title":"Interleukin 33 is induced by tumor necrosis factor alpha and interferon gamma in keratinocytes and contributes to allergic contact dermatitis","volume":"23","author":"Taniguchi","year":"2013","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1038\/jid.2012.185","article-title":"Regulation of IL-33 expression by IFN-\u03b3 and tumor necrosis factor-\u03b1 in normal human epidermal keratinocytes","volume":"132","author":"Meephansan","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jdermsci.2016.11.002","article-title":"Identification of the promoter region of human IL-33 responsive to induction by IFN\u03b3","volume":"85","author":"Tsuda","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jdermsci.2013.04.014","article-title":"Expression of IL-33 in the epidermis: The mechanism of induction by IL-17","volume":"71","author":"Meephansan","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1089\/jir.2015.0159","article-title":"The expression and regulation of interleukin-33 in human epidermal keratinocytes: A new mediator of atopic dermatitis and its possible signaling pathway","volume":"36","author":"Du","year":"2016","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tsuji, G., Hashimoto-Hachiya, A., Yen, V.H., Miake, S., Takemura, M., Mitamura, Y., Ito, T., Murata, M., Furue, M., and Nakahara, T. (2020). Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030891"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Furue, M. (2020). Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13\/IL-4\u2013JAK\u2013STAT6\/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9113741"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.alit.2016.12.002","article-title":"Atopic Dermatitis: Immune Deviation, Barrier Dysfunction, IgE Autoreactivity and New Therapies","volume":"66","author":"Furue","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/1346-8138.15664","article-title":"Basics and Recent Advances in the Pathophysiology of Atopic Dermatitis","volume":"48","author":"Nakahara","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/1346-8138.14486","article-title":"Microbiome Analysis of Forehead Skin in Patients with Atopic Dermatitis and Healthy Subjects: Implication of Staphylococcus and Corynebacterium","volume":"45","author":"Furue","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Na, C.H., Chung, J., and Simpson, E.L. (2019). Quality of Life and Disease Impact of Atopic Dermatitis and Psoriasis on Children and Their Families. Children, 6.","DOI":"10.3390\/children6120133"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/1346-8138.15507","article-title":"Pathogenic Implication of Epidermal Scratch Injury in Psoriasis and Atopic Dermatitis","volume":"47","author":"Furue","year":"2020","journal-title":"J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1111\/1346-8138.13392","article-title":"Committee for Clinical Practice Guidelines for the Management of Atopic Dermatitis of Japanese Dermatological Association. Clinical Practice Guidelines for the Management of Atopic Dermatitis 2016","volume":"43","author":"Saeki","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/exd.12967","article-title":"Distinct Molecular Signatures of Mild Extrinsic and Intrinsic Atopic Dermatitis","volume":"25","author":"Martel","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/sj.jid.5700630","article-title":"Filaggrin Mutations Strongly Predispose to Early-Onset and Extrinsic Atopic Dermatitis","volume":"127","author":"Weidinger","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000527007","article-title":"Guidelines for the Management of Atopic Dermatitis in Children: A Systematic Review","volume":"184","author":"Wang","year":"2023","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13921","DOI":"10.1073\/pnas.1307321110","article-title":"Skin-Specific Expression of IL-33 Activates Group 2 Innate Lymphoid Cells and Elicits Atopic Dermatitis-like Inflammation in Mice","volume":"110","author":"Imai","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2735","DOI":"10.1038\/cddis.2017.90","article-title":"Experimental Atopic Dermatitis Depends on IL-33R Signaling via MyD88 in Dendritic Cells","volume":"8","author":"Li","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/jid.2011.446","article-title":"IL-33 and ST2 in Atopic Dermatitis: Expression Profiles and Modulation by Triggering Factors","volume":"132","author":"Savinko","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jaad.2014.01.867","article-title":"Increased Serum Levels of Interleukin 33 in Patients with Atopic Dermatitis","volume":"70","author":"Okuzawa","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.alit.2023.01.002","article-title":"ILC2s in Skin Disorders","volume":"72","author":"Imai","year":"2023","journal-title":"Allergol. Int."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Furue, M. (2020). Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155382"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jid.2021.05.033","article-title":"Nuclear IL-33 Plays an Important Role in IL-31\u2013Mediated Downregulation of FLG, Keratin 1, and Keratin 10 by Regulating Signal Transducer and Activator of Transcription 3 Activation in Human Keratinocytes","volume":"142","author":"Dai","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1016\/j.jid.2021.04.002","article-title":"Nuclear IL-33 Plays an Important Role in the Suppression of FLG, LOR, Keratin 1, and Keratin 10 by IL-4 and IL-13 in Human Keratinocytes","volume":"141","author":"Dai","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Murdaca, G., Greco, M., Tonacci, A., Negrini, S., Borro, M., Puppo, F., and Gangemi, S. (2019). IL-33\/IL-31 Axis in Immune-Mediated and Allergic Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235856"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fmed.2017.00051","article-title":"Understanding Interleukin 33 and Its Roles in Eosinophil Development","volume":"2","author":"Johnston","year":"2017","journal-title":"Front. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.molimm.2014.06.018","article-title":"The Role of the IL-33\/IL-1RL1 Axis in Mast Cell and Basophil Activation in Allergic Disorders","volume":"63","author":"Saluja","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Furue, M., Furue, K., Tsuji, G., and Nakahara, T. (2020). Interleukin-17A and Keratinocytes in Psoriasis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041275"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"418","DOI":"10.23736\/S0392-0488.18.06202-8","article-title":"Psoriasis and the TNF\/IL23\/IL17 Axis","volume":"154","author":"Furue","year":"2019","journal-title":"G. Ital. Dermatol. Venereol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.2147\/CCID.S364640","article-title":"Guselkumab, Risankizumab, and Tildrakizumab in the Management of Psoriasis: A Review of the Real-World Evidence","volume":"15","author":"Ruggiero","year":"2022","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1080\/14712598.2022.2132143","article-title":"Anti-IL 23 Biologics for the Treatment of Plaque Psoriasis","volume":"12","author":"Vu","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_56","first-page":"209","article-title":"Pharmacogenetics and Pharmacogenomics in Moderate-to-Severe Psoriasis","volume":"2","author":"Reolid","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.jid.2020.07.027","article-title":"An Autocrine Circuit of IL-33 in Keratinocytes Is Involved in the Progression of Psoriasis","volume":"141","author":"Zeng","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/ced.12670","article-title":"Serum IL-33 Levels Are Increased in Patients with Psoriasis","volume":"41","author":"Mitsui","year":"2016","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8465083","DOI":"10.1155\/2020\/8465083","article-title":"Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris","volume":"2020","author":"Borsky","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cyto.2017.07.022","article-title":"IL-33-Matured Dendritic Cells Promote Th17 Cell Responses via IL-1\u03b2 and IL-6","volume":"99","author":"Park","year":"2017","journal-title":"Cytokine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/jdv.15450","article-title":"Itch: An Under-recognized Problem in Psoriasis","volume":"33","author":"Elewski","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s12264-017-0124-3","article-title":"TNF-\u03b1\/TNFR1 Signaling Is Required for the Full Expression of Acute and Chronic Itch in Mice via Peripheral and Central Mechanisms","volume":"34","author":"Miao","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1111\/exd.14206","article-title":"IL-23 Modulates Histamine-Evoked Itch and Responses of Pruriceptors in Mice","volume":"29","author":"Pavlenko","year":"2020","journal-title":"Exp. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/glia.23639","article-title":"Spinal IL-33\/ST2 Signaling Mediates Chronic Itch in Mice through the Astrocytic JAK2-STAT3 Cascade","volume":"67","author":"Du","year":"2019","journal-title":"Glia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2147\/CCID.S257647","article-title":"IL-33\/13 Axis and IL-4\/31 Axis Play Distinct Roles in Inflammatory Process and Itch in Psoriasis and Atopic Dermatitis","volume":"13","author":"Bodoor","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/jdv.16563","article-title":"Identification of a TH 2-High Psoriasis Cluster Based on Skin Biomarker Analysis in a Chinese Psoriasis Population","volume":"35","author":"Chen","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ni.1944","article-title":"IL-37 Is a Fundamental Inhibitor of Innate Immunity","volume":"11","author":"Nold","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/imr.12605","article-title":"Suppression of Inflammation and Acquired Immunity by IL-37","volume":"281","author":"Cavalli","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"696605","DOI":"10.3389\/fimmu.2021.696605","article-title":"Current Understanding of IL-37 in Human Health and Disease","volume":"12","author":"Su","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/ni.3103","article-title":"IL-37 Requires the Receptors IL-18R\u03b1 and IL-1R8 (SIGIRR) to Carry Out Its Multifaceted Anti-inflammatory Program upon Innate Signal Transduction","volume":"16","author":"Lo","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1073\/pnas.1324140111","article-title":"Role of Caspase-1 in Nuclear Translocation of IL-37, Release of the Cytokine, and IL-37 Inhibition of Innate Immune Responses","volume":"111","author":"Bulau","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Pan, Y., Wen, X., Hao, D., Wang, Y., Wang, L., He, G., and Jiang, X. (2020). The Role of IL-37 in Skin and Connective Tissue Diseases. Biomed. Pharmacother., 122.","DOI":"10.1016\/j.biopha.2019.109705"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e1151","DOI":"10.1002\/cnr2.1151","article-title":"IL-37: An Anti-inflammatory Cytokine with Antitumor Functions","volume":"2","author":"Mei","year":"2019","journal-title":"Cancer Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"15178","DOI":"10.1073\/pnas.1416714111","article-title":"Suppression of Antigen-Specific Adaptive Immunity by IL-37 via Induction of Tolerogenic Dendritic Cells","volume":"111","author":"Luo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hou, T., Tsang, M.S., Kan, L.L., Li, P., Chu, I.M., Lam, C.W., and Wong, C.K. (2021). IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147393"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jdermsci.2012.11.001","article-title":"Interleukin-37 Is Elevated in Subjects with Atopic Dermatitis","volume":"69","author":"Fujita","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1111\/all.14769","article-title":"Skewed Inflammation Is Associated with Aberrant Interleukin-37 Signaling Pathway in Atopic Dermatitis","volume":"76","author":"Hou","year":"2021","journal-title":"Allergy"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"830","DOI":"10.4049\/immunohorizons.2100055","article-title":"Transcriptomic Analysis of Healthy and Atopic Dermatitis Samples Reveals the Role of IL-37 in Human Skin","volume":"5","author":"Zhou","year":"2021","journal-title":"Immunohorizons."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1038\/jid.2014.28","article-title":"Transcriptome Analysis of Psoriasis in a Large Case-Control Sample: RNA-seq Provides Insights into Disease Mechanisms","volume":"134","author":"Li","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.4049\/jimmunol.1300047","article-title":"IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production","volume":"192","author":"Teng","year":"2014","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"754","DOI":"10.4049\/immunohorizons.2000083","article-title":"IL-37 Expression Is Downregulated in Lesional Psoriasis Skin","volume":"4","author":"Nielsen","year":"2020","journal-title":"Immunohorizons"},{"key":"ref_82","first-page":"179","article-title":"Evaluating Serum Levels of IL-33, IL-36, IL-37 and Gene Expression of IL-37 in Patients with Psoriasis Vulgaris","volume":"17","author":"Sehat","year":"2018","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.jaci.2015.12.1318","article-title":"Tofacitinib Attenuates Pathologic Immune Pathways in Patients with Psoriasis: A Randomized Phase 2 Study","volume":"137","author":"Krueger","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/jid.2011.24","article-title":"TNF-\u03b1 downregulates filaggrin and loricrin through c-Jun N-terminal kinase: Role for TNF-\u03b1 antagonists to improve skin barrier","volume":"131","author":"Kim","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jdermsci.2014.12.001","article-title":"Human \u03b2-defensin-3 increases the expression of interleukin-37 through CCR6 in human keratinocytes","volume":"77","author":"Smithrithee","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.4049\/jimmunol.1003162","article-title":"IL-1F5, -F6, -F8, and -F9: A novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression","volume":"186","author":"Johnston","year":"2011","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00403-014-1481-7","article-title":"Role of AhR\/ARNT systemin skin homeostasis","volume":"306","author":"Furue","year":"2014","journal-title":"Arch. Dermatol. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Furue, M., Uchi, H., Mitoma, C., Hashimoto-Hachiya, A., Chiba, T., Ito, T., Nakahara, T., and Tsuji, G. (2017). Antioxidants for Healthy Skin: The emerging role of aryl hydrocarbon receptors and nuclear factor-erythroid 2-related factor-2. Nutrients, 9.","DOI":"10.3390\/nu9030223"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0304-4165(02)00485-3","article-title":"Functional role of AhR in the expression of toxic effects by TCDD","volume":"1619","author":"Mimura","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_90","first-page":"42","article-title":"An environmental contaminant, benzo(a)pyrene, induces oxidative stress-mediated interleukin-8 production in human keratinocytes via the aryl hydrocarbon receptor signaling pathway","volume":"62","author":"Tsuji","year":"2011","journal-title":"J. Dermatol. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jid.2017.08.036","article-title":"Enhanced Expression of Genes Related to Xenobiotic Metabolism in the Skin of Patients with Atopic Dermatitis but Not with Ichthyosis Vulgaris","volume":"138","author":"Blunder","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/jid.2011.194","article-title":"Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: The basis of its anti-inflammatory effect","volume":"132","author":"Tsuji","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_93","first-page":"917","article-title":"Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis","volume":"123","author":"Bergboer","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/toxsci\/kfr218","article-title":"Exactly the same but different: Promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor","volume":"124","author":"Denison","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"35599","DOI":"10.1074\/jbc.M110.132043","article-title":"The aryl hydrocarbon receptor-interacting protein (AIP) is required for dioxin-induced hepatotoxicity but not for the induction of the Cyp1a1 and Cyp1a2 genes","volume":"285","author":"Nukaya","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"153154","DOI":"10.1016\/j.tox.2022.153154","article-title":"Aryl Hydrocarbon Receptor as a DNA Methylation Reader in the Stress Response Pathway","volume":"470","author":"Habano","year":"2022","journal-title":"Toxicology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/toxsci\/kfz114","article-title":"Interleukin 33 Expression Induced by Aryl Hydrocarbon Receptor in Macrophages","volume":"170","author":"Ishihara","year":"2019","journal-title":"Toxicol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2131\/jts.47.201","article-title":"Involvement of polycyclic aromatic hydrocarbons and endotoxin in macrophage expression of interleukin-33 induced by exposure to particulate matter","volume":"47","author":"Ishihara","year":"2022","journal-title":"J. Toxicol. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e20212397","DOI":"10.1084\/jem.20212397","article-title":"A dysregulated sebum-microbial metabolite-IL-33 axis initiates skin inflammation in atopic dermatitis","volume":"219","author":"Qiu","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"745997","DOI":"10.3389\/fimmu.2022.745997","article-title":"Natural Compounds Tapinarof and Galactomyces Ferment Filtrate Downregulate IL-33 Expression via the AHR\/IL-37 Axis in Human Keratinocytes","volume":"13","author":"Tsuji","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jaad.2018.06.047","article-title":"A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis","volume":"80","author":"Peppers","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.jaad.2022.06.1171","article-title":"One-year safety and efficacy of tapinarof cream for the treatment of plaque psoriasis: Results from the PSOARING 3 trial","volume":"87","author":"Strober","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Vu, Y.H., Hashimoto-Hachiya, A., Takemura, M., Yumine, A., Mitamura, Y., Nakahara, T., Furue, M., and Tsuji, G. (2020). IL-24 Negatively Regulates Keratinocyte Differentiation Induced by Tapinarof, an Aryl Hydrocarbon Receptor Modulator: Implication in the Treatment of Atopic Dermatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249412"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMoa2103629","article-title":"Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis","volume":"385","author":"Lebwohl","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e2931","DOI":"10.1038\/cddis.2017.322","article-title":"Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis","volume":"8","author":"Tsuji","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/ng.2438","article-title":"Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population","volume":"44","author":"Hirota","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/ng.1017","article-title":"Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis","volume":"44","author":"Paternoster","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.jid.2021.08.397","article-title":"Epidermis-Intrinsic Transcription Factor Ovol1 Coordinately Regulates Barrier Maintenance and Neutrophil Accumulation in Psoriasis-Like Inflammation","volume":"142","author":"Dragan","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3389\/fimmu.2019.00364","article-title":"IL33: Roles in Allergic Inflammation and Therapeutic Perspectives","volume":"10","author":"Chan","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Jeon, W.Y., Shin, H.K., Shin, I.S., Kim, S.K., and Lee, M.Y. (2015). Soshiho-tang Water Extract Inhibits Ovalbumin-Induced Airway Inflammation via the Regulation of Heme Oxygenase-1. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0857-3"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1248\/bpb.31.838","article-title":"Blockade of the Dioxin Pathway by Herbal Medicine Formula Bupleuri Minor: Identification of Active Entities for Suppression of AhR Activation","volume":"31","author":"Kasai","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1248\/yakushi.15-00153","article-title":"Aryl Hydrocarbon Receptor Ligand Activity of Extracts from 62 Herbal Medicines and Effect on Cytochrome P450 Activity","volume":"135","author":"Harada","year":"2015","journal-title":"Yakugaku Zasshi"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jep.2007.05.014","article-title":"The Potent Protective Effect of Wild Ginseng (Panax ginseng C.A. Meyer) against Benzo[alpha]pyrene-Induced Toxicity through Metabolic Regulation of CYP1A1 and GSTs","volume":"112","author":"Gum","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Che, D.N., Cho, B.O., Kim, J.S., Shin, J.Y., Kang, H.J., and Jang, S.I. (2020). Effect of Luteolin and Apigenin on the Production of Il-31 and Il-33 in Lipopolysaccharides-Activated Microglia Cells and Their Mechanism of Action. Nutrients, 12.","DOI":"10.3390\/nu12030811"},{"key":"ref_115","first-page":"2231","article-title":"Luteolin, an Aryl Hydrocarbon Receptor Ligand, Suppresses Tumor Metastasis In Vitro and In Vivo","volume":"44","author":"Feng","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/toxsci\/kfy075","article-title":"Structure-Dependent Modulation of Aryl Hydrocarbon Receptor-Mediated Activities by Flavonoids","volume":"164","author":"Jin","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6085801","DOI":"10.1155\/2019\/6085801","article-title":"PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes","volume":"2019","author":"Kim","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0031-9422(03)00142-0","article-title":"Actinidia arguta: Volatile Compounds in Fruit and Flowers","volume":"63","author":"Matich","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.foodchem.2018.07.084","article-title":"Anticholinergic Effects of Actinidia arguta Fruits and their Polyphenol Content Determined by Liquid Chromatography-Photodiode Array Detector-Quadrupole\/Time of Flight-Mass Spectrometry (LC-MS-PDA-Q\/TOF)","volume":"271","author":"Nowicka","year":"2019","journal-title":"Food Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1042\/bj3400715","article-title":"Dietary Flavonols Quercetin and Kaempferol Are Ligands of the Aryl Hydrocarbon Receptor that Affect CYP1A1 Transcription Differentially","volume":"340","author":"Ciolino","year":"1999","journal-title":"Biochem. J."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/exd.14217","article-title":"Early Transcriptional Changes after UVB Treatment in Atopic Dermatitis Include Inverse Regulation of IL-36\u03b3 and IL-37","volume":"30","author":"Lossius","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cbi.2004.08.005","article-title":"Metabolic Fate of the Ah Receptor Ligand 6-Formylindolo[3,2-b]carbazole","volume":"149","author":"Bergander","year":"2004","journal-title":"Chem. Biol. Interact."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14633\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:59:40Z","timestamp":1760129980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":122,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914633"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914633","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]}}}