Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis
Psoriasis is a chronic inflammatory skin disease characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes. Autophagy plays a critical role in regulating the functions of immune cells, endothelial cells, and especially keratinocytes, contributing to the pathogenesis...
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Taylor & Francis Group
2025-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2025.2544061 |
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| author | Wei Zhao Kainan Liao Wei Song Jing Wang Chunlin Cai Fusheng Zhou Dandan Zang Deping Xu Haisheng Zhou |
| author_facet | Wei Zhao Kainan Liao Wei Song Jing Wang Chunlin Cai Fusheng Zhou Dandan Zang Deping Xu Haisheng Zhou |
| author_sort | Wei Zhao |
| collection | DOAJ |
| description | Psoriasis is a chronic inflammatory skin disease characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes. Autophagy plays a critical role in regulating the functions of immune cells, endothelial cells, and especially keratinocytes, contributing to the pathogenesis of psoriasis. However, the role of chaperone-mediated autophagy (CMA) in psoriatic keratinocytes has not been fully explored. Our study, for the first time, revealed that defective CMA is present in imiquimod (IMQ)-induced psoriasiform lesions. Importantly, activation of CMA significantly attenuated IMQ-induced phenotypes both in vitro and in vivo, including reduced skin lesion severity, decreased keratinocyte proliferation and differentiation, and lower cytokine secretion. Mechanistically, toll-like receptor 7 (TLR7), containing a specific KFERQ-like motif, is a substrate for CMA-mediated degradation. This process modulates IMQ-TLR7 signal activation in keratinocytes. CMA deficiency in psoriasis leads to increased TLR7 levels, which, in turn, enhances TLR7-NF-κB signaling pathway activation, ultimately contributing to dysregulated keratinocyte proliferation, differentiation, and cytokine secretion. This study provides novel evidence that defective CMA is present in IMQ-induced psoriasiform lesions and that CMA activation can attenuate IMQ-induced phenotypes by modulating TLR7 signaling in keratinocytes. These findings highlight the potential of CMA as a therapeutic target for psoriasis. |
| format | Article |
| id | doaj-art-a4af41077dcd4e6ea692eaf7c82cbe90 |
| institution | Kabale University |
| issn | 2769-4127 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-a4af41077dcd4e6ea692eaf7c82cbe902025-08-25T12:17:46ZengTaylor & Francis GroupAutophagy Reports2769-41272025-12-014110.1080/27694127.2025.2544061Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitisWei Zhao0Kainan Liao1Wei Song2Jing Wang3Chunlin Cai4Fusheng Zhou5Dandan Zang6Deping Xu7Haisheng Zhou8Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Anhui Medical University, Hefei, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Anhui Medical University, Hefei, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Anhui Medical University, Hefei, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Anhui Medical University, Hefei, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, ChinaKey Laboratory of Dermatology, Anhui Medical University & Ministry of Education, Hefei, ChinaCenter for Scientific Research, Anhui Medical University, Hefei, ChinaClinical Laboratory, The second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Anhui Medical University, Hefei, ChinaPsoriasis is a chronic inflammatory skin disease characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes. Autophagy plays a critical role in regulating the functions of immune cells, endothelial cells, and especially keratinocytes, contributing to the pathogenesis of psoriasis. However, the role of chaperone-mediated autophagy (CMA) in psoriatic keratinocytes has not been fully explored. Our study, for the first time, revealed that defective CMA is present in imiquimod (IMQ)-induced psoriasiform lesions. Importantly, activation of CMA significantly attenuated IMQ-induced phenotypes both in vitro and in vivo, including reduced skin lesion severity, decreased keratinocyte proliferation and differentiation, and lower cytokine secretion. Mechanistically, toll-like receptor 7 (TLR7), containing a specific KFERQ-like motif, is a substrate for CMA-mediated degradation. This process modulates IMQ-TLR7 signal activation in keratinocytes. CMA deficiency in psoriasis leads to increased TLR7 levels, which, in turn, enhances TLR7-NF-κB signaling pathway activation, ultimately contributing to dysregulated keratinocyte proliferation, differentiation, and cytokine secretion. This study provides novel evidence that defective CMA is present in IMQ-induced psoriasiform lesions and that CMA activation can attenuate IMQ-induced phenotypes by modulating TLR7 signaling in keratinocytes. These findings highlight the potential of CMA as a therapeutic target for psoriasis.https://www.tandfonline.com/doi/10.1080/27694127.2025.2544061Chaperone-mediated autophagykeratinocyteNF-κBpsoriasistoll-like receptor 7 |
| spellingShingle | Wei Zhao Kainan Liao Wei Song Jing Wang Chunlin Cai Fusheng Zhou Dandan Zang Deping Xu Haisheng Zhou Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis Autophagy Reports Chaperone-mediated autophagy keratinocyte NF-κB psoriasis toll-like receptor 7 |
| title | Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis |
| title_full | Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis |
| title_fullStr | Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis |
| title_full_unstemmed | Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis |
| title_short | Chaperone-mediated autophagy dysfunction in imiquimod-induced psoriasiform dermatitis |
| title_sort | chaperone mediated autophagy dysfunction in imiquimod induced psoriasiform dermatitis |
| topic | Chaperone-mediated autophagy keratinocyte NF-κB psoriasis toll-like receptor 7 |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2025.2544061 |
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