CD8 T Cell‐Derived Exosomal miR‐186‐5p Elicits Renal Inflammation via Activating Tubular TLR7/8 Signal Axis
Abstract: 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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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CD8 T Cell‐Derived Exosomal miR‐186‐5p Elicits Renal Inflammation via Activating Tubular TLR7/8 Signal Axis ; day:03 ; month:07 ; year:2023 ; extent:15
Advanced science ; (03.07.2023) (gesamt 15)
- Creator
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Xu, Xiaodong
Qu, Shuang
Zhang, Changming
Zhang, Mingchao
Qin, Weisong
Ren, Guisheng
Bao, Hao
Li, Limin
Zen, Ke
Liu, Zhihong
- DOI
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10.1002/advs.202301492
- URN
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urn:nbn:de:101:1-2023070315321893702092
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 11:03 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Xu, Xiaodong
- Qu, Shuang
- Zhang, Changming
- Zhang, Mingchao
- Qin, Weisong
- Ren, Guisheng
- Bao, Hao
- Li, Limin
- Zen, Ke
- Liu, Zhihong
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