哈佛干细胞研究所David T. Scadden研究团队在研究中取得进展。他们的最新研究揭示了间充质胸腺生态位细胞可促进成年胸腺的再生和T细胞免疫。相关论文发表在2025年10月30日出版的《自然—生物技术》杂志上。

在这里，该团队证明了三种间充质细胞亚群中的一种是T淋巴细胞生成的关键生态位组成部分。Postn+亚群位于血管周围，其耗竭可能通过趋化因子Ccl19的产生而消除T细胞祖细胞的募集。随着年龄的增长，在急性造血干细胞移植条件下，它明显下降。当分离并过继转移后，Postn⁺细胞持久地植入萎缩的胸腺，招募早期T祖细胞，增加T细胞新生并增强T细胞对疫苗接种的反应。更容易获得的表达Ccl19的间充质群体也有类似的效果。这些数据定义了一种胸腺淋巴生态位细胞类型，可以通过治疗来再生T淋巴系统。

据介绍，胸腺萎缩及其伴随的进行性免疫衰退是一个主要的健康问题，慢性随年龄增长，急性随免疫损伤。目前尚无明确的解决办法。

附：英文原文

Title: Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity

Author: Gustafsson, Karin, Isaev, Sergey, Mirsanaye, Kamdin, Hofmann, Johanna, Kooshesh, Kameron A., Baryawno, Ninib, Kiem, Anna, Severe, Nicolas, Zhao, Ting, Scadden, Elizabeth W., Spencer, Joel A., Burns, Christian, Akilan, Kumaran, Barkas, Nikolaos, Gessessew, Hayalneh, Kokkaliaris, Konstantinos D., Lin, Charles P., Kharchenko, Peter V., Scadden, David T.

Issue&Volume: 2025-10-30

Abstract: Thymic atrophy and the progressive immune decline that accompanies it is a major health problem, chronically with age and acutely with immune injury. No definitive solution is available. Here we demonstrate that one of the three mesenchymal cell subsets identified by single-cell analysis of human and mouse thymic stroma is a critical niche component for T lymphopoiesis. The Postn+ subset is perivascular, and its depletion abrogates T cell progenitor recruitment, likely through production of the chemokine Ccl19. It markedly declines with age and in the acute setting of hematopoietic stem cell transplant conditioning. When isolated and adoptively transferred, Postn+ cells durably engraft the atrophic thymus, recruit early T progenitors, increase T cell neogenesis and enhance T cell response to vaccination. More readily available mesenchymal populations expressing Ccl19 provide similar effects. These data define a thymus lymphopoietic niche cell type that may be manipulated therapeutically to regenerate T lymphopoiesis.

DOI: 10.1038/s41587-025-02864-w

Source: https://www.nature.com/articles/s41587-025-02864-w