2. Academic Validation
  3. Cryptochrome 2 stabilization alleviates psoriasis by inhibiting keratinocyte hyperproliferation and inflammation

Cryptochrome 2 stabilization alleviates psoriasis by inhibiting keratinocyte hyperproliferation and inflammation

  • Int Immunopharmacol. 2026 Jan 1;168(Pt 1):115766. doi: 10.1016/j.intimp.2025.115766.
Lingling Yao 1,  Lian Cui 2,  Qianyu Chen 2,  Bingjie Li 3,  Zengyang Yu 4,  Zeyu Chen 2,  Yuxiong Jiang 2,  Zhuolin Guo 2,  Yuanyuan Wang 2,  Jiangluyi Cai 2,  Hao Mei 2,  Xilin Zhang 2,  Jing Zhou 5,  Chunyuan Guo 6,  Yuling Shi 7
Affiliations

Affiliations

  • 1 Department of Dermatology, Shanghai Skin Disease Hospital,Tongji University School of Medicine, Shanghai 201203, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai 201203, China; Laboratory of Laser and Medical Innovation Application, Department of Dermatology, Gongli Hospital of Shanghai Pudong New Area, 219 Miaopu Road, Pudong New District, Shanghai, China.
  • 2 Department of Dermatology, Shanghai Skin Disease Hospital,Tongji University School of Medicine, Shanghai 201203, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai 201203, China.
  • 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 201203, China.
  • 5 Department of Dermatology, Shanghai Skin Disease Hospital,Tongji University School of Medicine, Shanghai 201203, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai 201203, China. Electronic address: [email protected].
  • 6 Department of Dermatology, Shanghai Skin Disease Hospital,Tongji University School of Medicine, Shanghai 201203, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai 201203, China. Electronic address: [email protected].
  • 7 Department of Dermatology, Shanghai Skin Disease Hospital,Tongji University School of Medicine, Shanghai 201203, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai 201203, China. Electronic address: [email protected].
PMID: 41242269 DOI: 10.1016/j.intimp.2025.115766
Abstract

Psoriasis, a chronic inflammatory skin disorder, is characterized by aberrant keratinocyte proliferation and immune dysregulation. Although Cryptochrome 2 (CRY2), a circadian rhythm regulator, has been implicated in inflammatory conditions, its role in the psoriasis pathogenesis remains elusive. Here, we report a marked downregulation of CRY2 expression in psoriasis, which was reversed upon biological therapy, suggesting its pivotal involvement in disease progression. Using cellular, murine, and in vitro human tissue models, we revealed that CRY2 deficiency exacerbates inflammatory and hyperproliferative responses via ERK1/2 signaling activation. Furthermore，pharmacological stabilization of CRY2 using KL001 significantly ameliorated core psoriatic phenotypes, including epidermal thickening, proliferation marker expression, and chemokine production. These findings underscore CRY2 as a compelling therapeutic target in psoriasis, with KL001-mediated modulation offering potential as an adjunctive treatment strategy.

Keywords

Circadian rhythm; Cryptochrome 2; ERK1/2; Psoriasis.

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