Stem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice
© 2024. The Author(s)..
As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 08. März, Seite 2120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chi, Ani [VerfasserIn] |
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| Links: |
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| Themen: |
3XMK78S47O |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 12.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-46190-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369487443 |
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| 520 | |a As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders | ||
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| 700 | 1 | |a Mo, Jiahui |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhihong |e verfasserin |4 aut | |
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| 700 | 1 | |a Ma, Menghui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yanqing |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hanchao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhenqing |e verfasserin |4 aut | |
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| 700 | 1 | |a Liao, Yan |e verfasserin |4 aut | |
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| 700 | 1 | |a Deng, Chunhua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
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