Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies. Methods: This study invest...

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Main Authors: Yin-hong Zhang, Juan Chen, Wen-fei Mao, Li-xi Yan, Fei Long, Sheng-hao Li, Rui-xian Zhang
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Immunobiology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0171298525000191
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author Yin-hong Zhang
Juan Chen
Wen-fei Mao
Li-xi Yan
Fei Long
Sheng-hao Li
Rui-xian Zhang
author_facet Yin-hong Zhang
Juan Chen
Wen-fei Mao
Li-xi Yan
Fei Long
Sheng-hao Li
Rui-xian Zhang
author_sort Yin-hong Zhang
collection DOAJ
description Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies. Methods: This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays. Results: SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect. Conclusion: ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.
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spelling doaj-art-1250f0f9aae54e87a384f6e6c296ce2a2025-08-20T02:32:33ZengElsevierImmunobiology0171-29852025-05-01230315288510.1016/j.imbio.2025.152885Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE PatientsYin-hong Zhang0Juan Chen1Wen-fei Mao2Li-xi Yan3Fei Long4Sheng-hao Li5Rui-xian Zhang6Department of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Kunming Medical University, ChinaDepartment of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, ChinaDepartment of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, ChinaDepartment of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, ChinaThe Third People's Hospital of Kunming/Yunnan Clinical Center for Infectious Diseases, China; Corresponding author at: The Third People's Hospital of Kunming/Yunnan Clinical Center for Infectious Diseases, No.319 Wujing Road, Guandu District, Kunming City 650041, China.Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, China; Corresponding author at: The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Xishan District, Kunming, Yunnan Province 650032, China.Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies. Methods: This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays. Results: SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect. Conclusion: ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.http://www.sciencedirect.com/science/article/pii/S0171298525000191SLEADSC-exosTh17/TregmiR-16-5pLATS1
spellingShingle Yin-hong Zhang
Juan Chen
Wen-fei Mao
Li-xi Yan
Fei Long
Sheng-hao Li
Rui-xian Zhang
Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
Immunobiology
SLE
ADSC-exos
Th17/Treg
miR-16-5p
LATS1
title Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
title_full Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
title_fullStr Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
title_full_unstemmed Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
title_short Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
title_sort harnessing mir 16 5p loaded exosomes from adipose derived stem cells to restore immune homeostasis in sle patients
topic SLE
ADSC-exos
Th17/Treg
miR-16-5p
LATS1
url http://www.sciencedirect.com/science/article/pii/S0171298525000191
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