2. Academic Validation
  3. Limosilactobacillus reuteri CCFM1040 extracellular vesicles alleviate atopic dermatitis through signal transducer and activator of transcription STAT3-dependent modulation of epithelial cytokine

Limosilactobacillus reuteri CCFM1040 extracellular vesicles alleviate atopic dermatitis through signal transducer and activator of transcription STAT3-dependent modulation of epithelial cytokine

  • Int J Biol Macromol. 2025 Oct 30:148671. doi: 10.1016/j.ijbiomac.2025.148671.
Mohan Li 1,  Bingyong Mao 1,  Baojing Ren 1,  Borong Chen 1,  Xin Tang 1,  Qiuxiang Zhang 1,  Jianxin Zhao 2,  Wei Chen 3,  Shumao Cui 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Food Science and Resources, Jiangnan University, 214122 Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China.
  • 2 State Key Laboratory of Food Science and Resources, Jiangnan University, 214122 Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China; MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of medicine, Jiangnan University, 214122, Wuxi, Jiangsu, China.
  • 3 State Key Laboratory of Food Science and Resources, Jiangnan University, 214122 Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China; National Engineering Research Center for Functional Food, Jiangnan University, 214122, Wuxi, Jiangsu, China. Electronic address: chenwei66@jiangnan.edu.cn.
  • 4 State Key Laboratory of Food Science and Resources, Jiangnan University, 214122 Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China; International Joint Research Laboratory for Maternal-Infant Microbiota and Health, Jiangnan University, 214122, Wuxi, Jiangsu, China; Wuxi Institute for Specialized nutrition and Health Co., Ltd, 214112, Wuxi, Jiangsu, China.
PMID: 41175997 DOI: 10.1016/j.ijbiomac.2025.148671
Abstract

Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation and intense pruritus. Although the efficacy of Lactobacillus in AD management has been well-documented, the direct impact on skin remains unclear due to the limitations imposed by the intestinal barrier. Extracellular vesicles (EVs) derived from Lactobacillus exhibit superior membrane permeability, enabling them to potentially bypass gastrointestinal barriers and reach distant tissues. Through integrated murine model experiments and HaCaT Cell Analysis, we systematically evaluate the therapeutic potential of extracellular vesicles derived from Limosilactobacillus reuteri CCFM1040 (Lr1040-EVs) in AD pathophysiology. Our findings reveal that Lr1040-EVs significantly accelerate HaCaT cell migration while exerting potent anti-inflammatory and antipruritic effects through modulation of the signal transducer and activator of transcription 3 (STAT3) pathway. These effects were specifically manifested in the upregulation of barrier proteins (Occludin, Claudin7, filaggrin (FLG), loricrin (LOR)), enhancement of IL-10, and suppression of TNF-α and Th2-associated immune mediators. Proteomic analysis revealed that the bioactivity of Lr1040-EVs primarily originates from proteins associated with aminoacyl tRNA and biosynthesis. Histidyl tRNA synthetase has been verified to be one of the functional cargoes. Collectively, these results underscore the therapeutic efficacy of Lr1040-EVs in AD and elucidate their underlying molecular mechanisms, paving the way for clinical use and further study of their immunomodulatory effects.

Keywords

Atopic dermatitis; Limosilactobacillus reuteri CCFM1040-derived EVs (Lr1040-EVs); STAT3 pathway.

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