氯膦酸鹽脂質(zhì)體清除巨噬細胞受調(diào)節(jié)性 T 細胞 （Tregs） 調(diào)節(jié)來組織修復(fù)和再生

中文摘要：

調(diào)節(jié)性 T 細胞 （Tregs） 是組織修復(fù)和再生的關(guān)鍵免疫細胞。然而，它們作為基于細胞的再生療法的潛力尚未充分了解。在這里，我們表明外源性 Treg 到受傷的小鼠骨骼、肌肉和皮膚的局部遞送極大地促進了組織愈合。從機制上講，外源性 Treg 迅速采用損傷特異性表型來響應(yīng)受損的組織微環(huán)境，上調(diào)參與免疫調(diào)節(jié)和組織愈合的基因。我們證明，外源性 Tregs 通過直接或間接調(diào)節(jié)受傷組織中的單核細胞/巨噬細胞 （Mo/MΦ） 來發(fā)揮其再生作用，通過白細胞介素 （IL）-10 等因子促進它們轉(zhuǎn)變?yōu)榭寡缀痛儆鸂顟B(tài)。驗證 IL-10 在外源性 Treg 介導(dǎo)的修復(fù)和再生中的關(guān)鍵作用，當(dāng) IL10 被敲除時，這些細胞的促愈合能力就會喪失。此外，外源性 Treg 可減少受損組織中中性粒細胞和細胞毒性 T 細胞的積累以及 IFN-γ 的產(chǎn)生，進一步抑制促炎性 Mo/MΦ 表型。強調(diào)這種方法的潛力，我們證明了同種異體和人類 Treg 也可以促進組織愈合。總之，這項研究將外源性 Tregs 確立為再生醫(yī)學(xué)中一種可能的基于細胞的通用療法，并提供了關(guān)鍵的機制見解，可用于開發(fā)基于免疫細胞的療法以增強組織愈合。

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.

論文信息：

論文題目：Local administration of regulatory T cells promotes tissue healing

期刊名稱：Nature Communications

時間期卷：15, Article number: 7863 (2024)

在線時間：2024年9月9日

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

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點科技）

氯膦酸鹽脂質(zhì)體清除皮膚，肌肉和骨巨噬細胞。外源性Tregs通過直接或間接調(diào)節(jié)受傷組織中的單核細胞/巨噬細胞 （Mo/MΦ） 來發(fā)揮其再生作用，通過白細胞介素 （IL）-10 等因子促進它們轉(zhuǎn)變?yōu)榭寡缀痛儆鸂顟B(tài)。氯膦酸鹽二鈉脂質(zhì)體清除巨噬細胞在損傷修復(fù)模型Treg細胞功能研究，荷蘭Liposoma巨噬細胞清除劑Clodronate Liposomes見刊于Nature Communications：調(diào)節(jié)性 T 細胞 （Tregs） 是組織修復(fù)和再生的關(guān)鍵免疫細胞。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

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.