氯膦酸盐脂质体清除巨噬细胞受调节性 T 细胞 （Tregs） 调节来组织修复和再生

中文摘要：

调节性 T 细胞 （Tregs） 是组织修复和再生的关键免疫细胞。然而，它们作为基于细胞的再生疗法的潜力尚未充分了解。在这里，我们表明外源性 Treg 到受伤的小鼠骨骼、肌肉和皮肤的局部递送极大地促进了组织愈合。从机制上讲，外源性 Treg 迅速采用损伤特异性表型来响应受损的组织微环境，上调参与免疫调节和组织愈合的基因。我们证明，外源性 Tregs 通过直接或间接调节受伤组织中的单核细胞/巨噬细胞 （Mo/MΦ） 来发挥其再生作用，通过白细胞介素 （IL）-10 等因子促进它们转变为抗炎和促愈状态。验证 IL-10 在外源性 Treg 介导的修复和再生中的关键作用，当 IL10 被敲除时，这些细胞的促愈合能力就会丧失。此外，外源性 Treg 可减少受损组织中中性粒细胞和细胞毒性 T 细胞的积累以及 IFN-γ 的产生，进一步抑制促炎性 Mo/MΦ 表型。强调这种方法的潜力，我们证明了同种异体和人类 Treg 也可以促进组织愈合。总之，这项研究将外源性 Tregs 确立为再生医学中一种可能的基于细胞的通用疗法，并提供了关键的机制见解，可用于开发基于免疫细胞的疗法以增强组织愈合。

英文摘要：

Regulatory T cells (Tregs) are crucial immune cells for tissue repair and regeneration. However, their potential as a cell-based regenerative therapy is not yet fully understood. Here, we show that local delivery of exogenous Tregs into injured mouse bone, muscle, and skin greatly enhances tissue healing. Mechanistically, exogenous Tregs rapidly adopt an injury-specific phenotype in response to the damaged tissue microenvironment, upregulating genes involved in immunomodulation and tissue healing. We demonstrate that exogenous Tregs exert their regenerative effect by directly and indirectly modulating monocytes/macrophages (Mo/MΦ) in injured tissues, promoting their switch to an anti-inflammatory and pro-healing state via factors such as interleukin (IL)-10. Validating the key role of IL-10 in exogenous Treg-mediated repair and regeneration, the pro-healing capacity of these cells is lost when Il10 is knocked out. Additionally, exogenous Tregs reduce neutrophil and cytotoxic T cell accumulation and IFN-γ production in damaged tissues, further dampening the pro-inflammatory Mo/MΦ phenotype. Highlighting the potential of this approach, we demonstrate that allogeneic and human Tregs also promote tissue healing. Together, this study establishes exogenous Tregs as a possible universal cell-based therapy for regenerative medicine and provides key mechanistic insights that could be harnessed to develop immune cell-based therapies to enhance tissue healing.

论文信息：

论文题目：Local administration of regulatory T cells promotes tissue healing

期刊名称：Nature Communications

时间期卷：15, Article number: 7863 (2024)

在线时间：2024年9月9日

DOI：doi.org/10.1038/s41467-024-51353-2

产品信息：

货号：CP-005-005

规格：5ml+5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes and Control Liposomes

办事处：Target Technology（靶点科技）

氯膦酸盐脂质体清除皮肤，肌肉和骨巨噬细胞。外源性Tregs通过直接或间接调节受伤组织中的单核细胞/巨噬细胞 （Mo/MΦ） 来发挥其再生作用，通过白细胞介素 （IL）-10 等因子促进它们转变为抗炎和促愈状态。氯膦酸盐二钠脂质体清除巨噬细胞在损伤修复模型Treg细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：调节性 T 细胞 （Tregs） 是组织修复和再生的关键免疫细胞。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

Macrophage depletion by CL

Ten-week-old male wildtype C57BL/6J mice received intraperitoneal injections of clodronate encapsulated in liposomes or control PBS liposomes (200 μl of 5 mg/ml) (Liposoma B.V., CP-005-005) 1 day before injury. Injections continued every other day until day 7 post-injury to deplete macrophages. Efficiency of macrophage depletion was validated by assessing F4/80+ macrophage levels within the CD11b+ myeloid cell population in spleen using flow cytometry.