2. Academic Validation
  3. LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea

LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea

  • Commun Biol. 2025 Oct 14;8(1):1470. doi: 10.1038/s42003-025-08861-8.
Wenyue Huang 1 2,  Hailun He 3,  Haien Wu 4,  Yichong Wang 1 2,  Jingyu Wang 2 5,  Yan Sun 2 5,  Hexiao Wang 2 5,  Shulan Yao 6,  Linlin Zhu 4,  Yi Jiang 7,  Xinze Cai # 8,  Yan Wu # 9 10
Affiliations

Affiliations

  • 1 Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.
  • 2 National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China.
  • 3 Department of Medical Aesthetics, The Third People's Hospital of Chengdu, Southwest Jiaotong University, Chengdu, China.
  • 4 Department of Dermatology, The Seventh People's Hospital of Shenyang, Shenyang, China.
  • 5 Department of Dermatology, The First Hospital of China Medical University, Shenyang, China.
  • 6 Department of Dermatology, Affiliated Hospital of Jining Medical University, Shandong, China.
  • 7 Central Laboratory, The First Hospital of China Medical University, Shenyang, China.
  • 8 Central Laboratory, The First Hospital of China Medical University, Shenyang, China. [email protected].
  • 9 Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China. [email protected].
  • 10 National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China. [email protected].
  • # Contributed equally.
PMID: 41087666 DOI: 10.1038/s42003-025-08861-8
Abstract

Rosacea is a chronic inflammatory skin disorder linked to the antimicrobial peptide LL-37 and immune cells. STING, a key DNA-sensing adaptor, initiates innate immune responses, with excessive activation contributing to inflammation. This study investigates LAPTM5, a STING-interacting protein, and its role in rosacea. We observe elevated nuclear DNA fragmentation within the dermal lesions of rosacea patients and LL-37-induced rosacea-like mice. LAPTM5 and STING levels are upregulated in macrophages within rosacea lesions and LL-37-induced models, along with STING hyperactivation. LAPTM5 knockdown in macrophages reduces STING protein levels, signaling, and inflammatory responses under DMXAA and HT-DNA stimulation. LAPTM5 associates with STING and represses its K48- and K63-linked polyubiquitination, preventing proteasomal and lysosomal degradation, thereby maintaining STING stability at homeostasis and after activation. Both STING antagonist H-151 and LAPTM5 knockdown alleviate LL-37-induced rosacea-like phenotypes. These findings highlight LAPTM5 as a STING stabilizer, aggravating STING-driven inflammation in rosacea, offering insights for potential treatments.

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