Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway
Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue-specific transgenic mice, various...
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2024
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| Online Access: | http://dx.doi.org/10.1016/j.jid.2024.01.025 https://www.sciencedirect.com/science/article/pii/S0022202X24001088 http://hdl.handle.net/10576/61709 |
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| _version_ | 1857415087494529024 |
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| author | Yanqing, Li |
| author2 | Chen, Weiwei Zhu, Xingyun Mei, Huiyuan Steinhoff, Martin Buddenkotte, Joerg Wang, Jinhai Zhang, Wenhao Li, Zhenghui Dai, Xiaolong Shan, Chunxu Wang, Jiafu Meng, Jianghui |
| author2_role | author author author author author author author author author author author author |
| author_facet | Yanqing, Li Chen, Weiwei Zhu, Xingyun Mei, Huiyuan Steinhoff, Martin Buddenkotte, Joerg Wang, Jinhai Zhang, Wenhao Li, Zhenghui Dai, Xiaolong Shan, Chunxu Wang, Jiafu Meng, Jianghui |
| author_role | author |
| dc.creator.none.fl_str_mv | Yanqing, Li Chen, Weiwei Zhu, Xingyun Mei, Huiyuan Steinhoff, Martin Buddenkotte, Joerg Wang, Jinhai Zhang, Wenhao Li, Zhenghui Dai, Xiaolong Shan, Chunxu Wang, Jiafu Meng, Jianghui |
| dc.date.none.fl_str_mv | 2024-12-08T08:49:15Z 2024-08-31 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.jid.2024.01.025 Li, Y., Chen, W., Zhu, X., Mei, H., Steinhoff, M., Buddenkotte, J., ... & Meng, J. (2024). Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway. Journal of Investigative Dermatology. 0022-202X https://www.sciencedirect.com/science/article/pii/S0022202X24001088 http://hdl.handle.net/10576/61709 8 144 1523-1747 |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Atopic dermatitis BST2 IL-27 itch PAR2 |
| dc.title.none.fl_str_mv | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue-specific transgenic mice, various itch models, behavior scoring, RNA sequencing, and cytokine/kinase array. Our findings show that IL-27 receptors were overexpressed in human AD skin. Intradermal IL-27 injection failed to directly induce itch in mice but upregulated skin protease-activated receptor 2 (PAR2) transcripts, a key factor in itch and AD. IL-27 activated human keratinocytes, increasing PAR2 transcription and activity. Coinjection of SLIGRL (PAR2 agonist) and IL-27 in mice heightened PAR2-mediated itch. In addition, IL-27 boosted BST2 transcription in sensory neurons and keratinocytes. BST2 was upregulated in AD skin, and its injection in mice induced itch-like response. BST2 colocalized with sensory nerve branches in AD skin from both human and murine models. Sensory neurons released BST2, and mice with sensory neuron–specific BST2 knockout displayed reduced itch responses. Overall, this study provides evidence that skin IL-27/PAR2 and neuronal IL-27/BST2 axes are implicated in cutaneous inflammation and pruritus. The discovery of neuronal BST2 in pruritus shed light on BST2 in the itch cascade. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_181a0ee6252ab4a3cfa37b4b4880a8ab |
| identifier_str_mv | Li, Y., Chen, W., Zhu, X., Mei, H., Steinhoff, M., Buddenkotte, J., ... & Meng, J. (2024). Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway. Journal of Investigative Dermatology. 0022-202X 8 144 1523-1747 |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/61709 |
| publishDate | 2024 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| spelling | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch PathwayYanqing, LiChen, WeiweiZhu, XingyunMei, HuiyuanSteinhoff, MartinBuddenkotte, JoergWang, JinhaiZhang, WenhaoLi, ZhenghuiDai, XiaolongShan, ChunxuWang, JiafuMeng, JianghuiAtopic dermatitisBST2IL-27itchPAR2Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue-specific transgenic mice, various itch models, behavior scoring, RNA sequencing, and cytokine/kinase array. Our findings show that IL-27 receptors were overexpressed in human AD skin. Intradermal IL-27 injection failed to directly induce itch in mice but upregulated skin protease-activated receptor 2 (PAR2) transcripts, a key factor in itch and AD. IL-27 activated human keratinocytes, increasing PAR2 transcription and activity. Coinjection of SLIGRL (PAR2 agonist) and IL-27 in mice heightened PAR2-mediated itch. In addition, IL-27 boosted BST2 transcription in sensory neurons and keratinocytes. BST2 was upregulated in AD skin, and its injection in mice induced itch-like response. BST2 colocalized with sensory nerve branches in AD skin from both human and murine models. Sensory neurons released BST2, and mice with sensory neuron–specific BST2 knockout displayed reduced itch responses. Overall, this study provides evidence that skin IL-27/PAR2 and neuronal IL-27/BST2 axes are implicated in cutaneous inflammation and pruritus. The discovery of neuronal BST2 in pruritus shed light on BST2 in the itch cascade.This worked is supported by a fund from National Natural Science of Foundation of China (NSFC 82273509), and a fund from LEO Foundation. It is also funded by National Priorities Research Program (NPRP11S-0117-180326) of the Qatar National Research Fund, Qatar Foundation; and Internal Research Grand Competition (IRGC-04-SI-17-151), MRC Fund, Hamad Medical Corporation, Qatar.Elsevier2024-12-08T08:49:15Z2024-08-31Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.jid.2024.01.025Li, Y., Chen, W., Zhu, X., Mei, H., Steinhoff, M., Buddenkotte, J., ... & Meng, J. (2024). Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway. Journal of Investigative Dermatology.0022-202Xhttps://www.sciencedirect.com/science/article/pii/S0022202X24001088http://hdl.handle.net/10576/6170981441523-1747enhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/617092024-12-08T19:05:28Z |
| spellingShingle | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway Yanqing, Li Atopic dermatitis BST2 IL-27 itch PAR2 |
| status_str | publishedVersion |
| title | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| title_full | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| title_fullStr | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| title_full_unstemmed | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| title_short | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| title_sort | Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27–Driven Itch Pathway |
| topic | Atopic dermatitis BST2 IL-27 itch PAR2 |
| url | http://dx.doi.org/10.1016/j.jid.2024.01.025 https://www.sciencedirect.com/science/article/pii/S0022202X24001088 http://hdl.handle.net/10576/61709 |