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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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2025.2544061 |
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| Summary: | 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. |
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| ISSN: | 2769-4127 |