Novel Therapeutic Targets for the Treatment of Atopic Dermatitis
Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to...
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MDPI AG
2023-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/5/1303 |
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| author | Gaku Tsuji Kazuhiko Yamamura Koji Kawamura Makiko Kido-Nakahara Takamichi Ito Takeshi Nakahara |
| author_facet | Gaku Tsuji Kazuhiko Yamamura Koji Kawamura Makiko Kido-Nakahara Takamichi Ito Takeshi Nakahara |
| author_sort | Gaku Tsuji |
| collection | DOAJ |
| description | Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to the recognition of multiple novel therapeutic targets. For systemic therapy, new biologic agents that target IL-13, IL-22, IL-33, the IL-23/IL-17 axis, and OX40-OX40L are being developed. Binding of type II cytokines to their receptors activates Janus kinase (JAK) and its downstream signal, namely signal transduction and activator of transcription (STAT). JAK inhibitors block the activation of the JAK-STAT pathway, thereby blocking the signaling pathways mediated by type II cytokines. In addition to oral JAK inhibitors, histamine H4 receptor antagonists are under investigation as small-molecule compounds. For topical therapy, JAK inhibitors, aryl hydrocarbon receptor modulators, and phosphodiesterase-4 inhibitors are being approved. Microbiome modulation is also being examined for the treatment of AD. This review outlines current and future directions for novel therapies of AD that are currently being investigated in clinical trials, focusing on their mechanisms of action and efficacy. This supports the accumulation of data on advanced treatments for AD in the new era of precision medicine. |
| first_indexed | 2024-03-11T03:55:44Z |
| format | Article |
| id | doaj.art-72a05b34c3134096ae319252c6a54be6 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:55:44Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-72a05b34c3134096ae319252c6a54be62023-11-18T00:35:01ZengMDPI AGBiomedicines2227-90592023-04-01115130310.3390/biomedicines11051303Novel Therapeutic Targets for the Treatment of Atopic DermatitisGaku Tsuji0Kazuhiko Yamamura1Koji Kawamura2Makiko Kido-Nakahara3Takamichi Ito4Takeshi Nakahara5Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka 812-8582, JapanResearch and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka 812-8582, JapanDepartment of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanResearch and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka 812-8582, JapanAtopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to the recognition of multiple novel therapeutic targets. For systemic therapy, new biologic agents that target IL-13, IL-22, IL-33, the IL-23/IL-17 axis, and OX40-OX40L are being developed. Binding of type II cytokines to their receptors activates Janus kinase (JAK) and its downstream signal, namely signal transduction and activator of transcription (STAT). JAK inhibitors block the activation of the JAK-STAT pathway, thereby blocking the signaling pathways mediated by type II cytokines. In addition to oral JAK inhibitors, histamine H4 receptor antagonists are under investigation as small-molecule compounds. For topical therapy, JAK inhibitors, aryl hydrocarbon receptor modulators, and phosphodiesterase-4 inhibitors are being approved. Microbiome modulation is also being examined for the treatment of AD. This review outlines current and future directions for novel therapies of AD that are currently being investigated in clinical trials, focusing on their mechanisms of action and efficacy. This supports the accumulation of data on advanced treatments for AD in the new era of precision medicine.https://www.mdpi.com/2227-9059/11/5/1303atopic dermatitisbiologicsmall-molecule inhibitor |
| spellingShingle | Gaku Tsuji Kazuhiko Yamamura Koji Kawamura Makiko Kido-Nakahara Takamichi Ito Takeshi Nakahara Novel Therapeutic Targets for the Treatment of Atopic Dermatitis Biomedicines atopic dermatitis biologic small-molecule inhibitor |
| title | Novel Therapeutic Targets for the Treatment of Atopic Dermatitis |
| title_full | Novel Therapeutic Targets for the Treatment of Atopic Dermatitis |
| title_fullStr | Novel Therapeutic Targets for the Treatment of Atopic Dermatitis |
| title_full_unstemmed | Novel Therapeutic Targets for the Treatment of Atopic Dermatitis |
| title_short | Novel Therapeutic Targets for the Treatment of Atopic Dermatitis |
| title_sort | novel therapeutic targets for the treatment of atopic dermatitis |
| topic | atopic dermatitis biologic small-molecule inhibitor |
| url | https://www.mdpi.com/2227-9059/11/5/1303 |
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