Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc..
BACKGROUND AIMS: The immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them a promising therapeutic approach for liver fibrosis (LF). Here, we postulated that MSCs could potentially suppress the pro-fibrotic activity of intrahepatic B cells, thereby inhibiting LF progression.
APPROACH RESULTS: Administration of MSCs significantly ameliorated LF as indicated by reduced myofibroblast activation, collagen deposition, and inflammation. The treatment efficacy of MSCs can be attributed to decreased infiltration, activation, and pro-inflammatory cytokine production of intrahepatic B cells. Single-cell RNA sequencing revealed a distinct intrahepatic B cell atlas and a subtype of naive B cells (B-II) was identified, which were markedly abundant in fibrotic liver, displaying mature features with elevated expression of several proliferative and inflammatory genes. Transcriptional profiling of total B cells revealed that intrahepatic B cells displayed activation, proliferation, and pro-inflammatory gene profile during LF. Fibrosis was attenuated in mice ablated with B cells (μMT) or in vivo treatment with anti-CD20. Moreover, fibrosis was recapitulated in μMT after adoptive transfer of B cells, which in turn could be rescued by MSC injection, validating the pathogenic function of B cells and the efficacy of MSCs on B cell-promoted LF progression. Mechanistically, MSCs could inhibit the proliferation and cytokine production of intrahepatic B cells through exosomes, regulating the MAPK and NF-kappa B signaling pathways.
CONCLUSIONS: Intrahepatic B-cell serve as a target of MSCs, play an important role in the process of MSC-induced amelioration of LF, and may provide new clues for revealing the novel mechanisms of MSC action.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Hepatology (Baltimore, Md.) - (2024) vom: 28. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Feng, Xudong [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 28.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1097/HEP.0000000000000831 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370358147 |
|---|
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| 245 | 1 | 0 | |a Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells |
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| 520 | |a Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. | ||
| 520 | |a BACKGROUND AIMS: The immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them a promising therapeutic approach for liver fibrosis (LF). Here, we postulated that MSCs could potentially suppress the pro-fibrotic activity of intrahepatic B cells, thereby inhibiting LF progression | ||
| 520 | |a APPROACH RESULTS: Administration of MSCs significantly ameliorated LF as indicated by reduced myofibroblast activation, collagen deposition, and inflammation. The treatment efficacy of MSCs can be attributed to decreased infiltration, activation, and pro-inflammatory cytokine production of intrahepatic B cells. Single-cell RNA sequencing revealed a distinct intrahepatic B cell atlas and a subtype of naive B cells (B-II) was identified, which were markedly abundant in fibrotic liver, displaying mature features with elevated expression of several proliferative and inflammatory genes. Transcriptional profiling of total B cells revealed that intrahepatic B cells displayed activation, proliferation, and pro-inflammatory gene profile during LF. Fibrosis was attenuated in mice ablated with B cells (μMT) or in vivo treatment with anti-CD20. Moreover, fibrosis was recapitulated in μMT after adoptive transfer of B cells, which in turn could be rescued by MSC injection, validating the pathogenic function of B cells and the efficacy of MSCs on B cell-promoted LF progression. Mechanistically, MSCs could inhibit the proliferation and cytokine production of intrahepatic B cells through exosomes, regulating the MAPK and NF-kappa B signaling pathways | ||
| 520 | |a CONCLUSIONS: Intrahepatic B-cell serve as a target of MSCs, play an important role in the process of MSC-induced amelioration of LF, and may provide new clues for revealing the novel mechanisms of MSC action | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Feng, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jiahang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jinfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Qiaoling |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jiong |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Dandan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lanjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Hongcui |e verfasserin |4 aut | |
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