CD8 T Cell-Derived Exosomal miR-186-5p Elicits Renal Inflammation via Activating Tubular TLR7/8 Signal Axis
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH..
T cells play an important role in the development of focal segmental glomerulosclerosis (FSGS). The mechanism underlying such T cell-based kidney disease, however, remains elusive. Here the authors report that activated CD8 T cells elicit renal inflammation and tissue injury via releasing miR-186-5p-enriched exosomes. Continuing the cohort study identifying the correlation of plasma level of miR-186-5p with proteinuria in FSGS patients, it is demonstrated that circulating miR-186-5p is mainly derived from activated CD8 T cell exosomes. Renal miR-186-5p, which is markedly increased in FSGS patients and mice with adriamycin-induced renal injury, is mainly delivered by CD8 T cell exosomes. Depleting miR-186-5p strongly attenuates adriamycin-induced mouse renal injury. Supporting the function of exosomal miR-186-5p as a key circulating pathogenic factor, intravenous injection of miR-186-5p or miR-186-5p-containing T cell exosomes results in mouse renal inflammation and tissue injury. Tracing the injected T cell exosomes shows their preferential distribution in mouse renal tubules, not glomerulus. Mechanistically, miR-186-5p directly activates renal tubular TLR7/8 signal and initiates tubular cell apoptosis. Mutating the TLR7-binding sequence on miR-186-5p or deleting mouse TLR7 largely abolishes renal tubular injuries induced by miR-186-5p or adriamycin. These findings reveal a causative role of exosomal miR-186-5p in T cell-mediated renal dysfunction.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 10(2023), 25 vom: 03. Sept., Seite e2301492 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Xiaodong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.09.2023 Date Revised 29.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202301492 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a T cells play an important role in the development of focal segmental glomerulosclerosis (FSGS). The mechanism underlying such T cell-based kidney disease, however, remains elusive. Here the authors report that activated CD8 T cells elicit renal inflammation and tissue injury via releasing miR-186-5p-enriched exosomes. Continuing the cohort study identifying the correlation of plasma level of miR-186-5p with proteinuria in FSGS patients, it is demonstrated that circulating miR-186-5p is mainly derived from activated CD8 T cell exosomes. Renal miR-186-5p, which is markedly increased in FSGS patients and mice with adriamycin-induced renal injury, is mainly delivered by CD8 T cell exosomes. Depleting miR-186-5p strongly attenuates adriamycin-induced mouse renal injury. Supporting the function of exosomal miR-186-5p as a key circulating pathogenic factor, intravenous injection of miR-186-5p or miR-186-5p-containing T cell exosomes results in mouse renal inflammation and tissue injury. Tracing the injected T cell exosomes shows their preferential distribution in mouse renal tubules, not glomerulus. Mechanistically, miR-186-5p directly activates renal tubular TLR7/8 signal and initiates tubular cell apoptosis. Mutating the TLR7-binding sequence on miR-186-5p or deleting mouse TLR7 largely abolishes renal tubular injuries induced by miR-186-5p or adriamycin. These findings reveal a causative role of exosomal miR-186-5p in T cell-mediated renal dysfunction | ||
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| 650 | 4 | |a T cells | |
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| 650 | 4 | |a circulating pathogenic factors | |
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| 700 | 1 | |a Qu, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Changming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Mingchao |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Weisong |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Guisheng |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Limin |e verfasserin |4 aut | |
| 700 | 1 | |a Zen, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhihong |e verfasserin |4 aut | |
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