Nature communications · 2024
Stem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Chi Ani, Yang Bicheng, Dai Hao, Li Xinyu, Mo Jiahui, Gao Yong, Chen Zhihong, Feng Xin, Ma Menghui, Li Yanqing, Yang Chao, Liu Jie, Liu Hanchao, Wang Zhenqing, Gao Feng, Liao Yan, Shi Xuetao, Deng Chunhua, Zhang Min
Аннотация
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.