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已发表论文
性别差异和雄激素调节塑造 SKG 关节炎模型中的黏膜免疫表型、肠道微生物群以及微生物群衍生的乳酸
Authors Wu X , Jiang L , Cao Y, Wang P, Wang W, Zhang X
Received 11 July 2025
Accepted for publication 30 October 2025
Published 14 November 2025 Volume 2025:18 Pages 15911—15924
DOI https://doi.org/10.2147/JIR.S552491
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Ujjwol Risal
Xinran Wu,1,* Lingjuan Jiang,2,3,* Yubin Cao,2 Peng Wang,2 Wenjing Wang,2 Xuan Zhang1
1Department of Rheumatology and Immunology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lingjuan Jiang, Email irisjlj@163.com Xuan Zhang, Email zxpumch2003@sina.com
Objective: This study aimed to investigate the role of sex differences and androgen regulation in the development of arthritis, focusing on their effects on gut microbiota, metabolic profiles, and immune responses in the SKG mouse model of arthritis.
Methods: Eight-week-old male and female SKG mice were injected with zymosan to explore sex-related differences in arthritis progression. Androgen regulation was assessed in 4-week-old male SKG mice through castration and sham surgeries. Flow cytometry, 16S rDNA sequencing, metabolomics, histopathology, and immunofluorescence were used to evaluate immune responses, microbiota composition, and metabolic alterations.
Results: Sex differences significantly impacted immune cell composition, particularly dendritic cells (DCs), in the mesenteric and popliteal lymph nodes. Male mice exhibited an increased proportion of conventional type I DCs (cDC1), while female mice displayed a higher proportion of conventional type II DCs (cDC2). Androgen deprivation in male mice worsened disease severity, with reduced cDC1 cells and increased inflammatory infiltration. Sex differences also influenced gut microbiota, with higher levels of Lactobacillus in females, and castrated males resembling females in microbiota composition. Metabolomic analysis revealed significant sex-related differences, with lactate showing the most pronounced androgen-related changes. Additionally, androgen regulated hypoxia inducible factor-1 alpha (HIF1α) expression in mucosal DCs, promoting an immune tolerance phenotype.
Conclusion: This study highlights the significant role of sex and androgen regulation in arthritis development, revealing complex interactions between hormones, microbiota, and immune regulation. These findings suggest new avenues for sex-specific therapeutic strategies and precision interventions targeting microbiota and metabolic modulation in arthritis and other autoimmune diseases.
Keywords: arthritis, androgen regulation, dendritic cells, gut microbiota, microbiota-derived lactate, immune tolerance
1Department of Rheumatology and Immunology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lingjuan Jiang, Email irisjlj@163.com Xuan Zhang, Email zxpumch2003@sina.com
Objective: This study aimed to investigate the role of sex differences and androgen regulation in the development of arthritis, focusing on their effects on gut microbiota, metabolic profiles, and immune responses in the SKG mouse model of arthritis.
Methods: Eight-week-old male and female SKG mice were injected with zymosan to explore sex-related differences in arthritis progression. Androgen regulation was assessed in 4-week-old male SKG mice through castration and sham surgeries. Flow cytometry, 16S rDNA sequencing, metabolomics, histopathology, and immunofluorescence were used to evaluate immune responses, microbiota composition, and metabolic alterations.
Results: Sex differences significantly impacted immune cell composition, particularly dendritic cells (DCs), in the mesenteric and popliteal lymph nodes. Male mice exhibited an increased proportion of conventional type I DCs (cDC1), while female mice displayed a higher proportion of conventional type II DCs (cDC2). Androgen deprivation in male mice worsened disease severity, with reduced cDC1 cells and increased inflammatory infiltration. Sex differences also influenced gut microbiota, with higher levels of Lactobacillus in females, and castrated males resembling females in microbiota composition. Metabolomic analysis revealed significant sex-related differences, with lactate showing the most pronounced androgen-related changes. Additionally, androgen regulated hypoxia inducible factor-1 alpha (HIF1α) expression in mucosal DCs, promoting an immune tolerance phenotype.
Conclusion: This study highlights the significant role of sex and androgen regulation in arthritis development, revealing complex interactions between hormones, microbiota, and immune regulation. These findings suggest new avenues for sex-specific therapeutic strategies and precision interventions targeting microbiota and metabolic modulation in arthritis and other autoimmune diseases.
Keywords: arthritis, androgen regulation, dendritic cells, gut microbiota, microbiota-derived lactate, immune tolerance