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胚胎干细胞来源的间充质干细胞通过调节肥大细胞和 T 细胞的功能缓解实验性接触性荨麻疹。

Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions of mast cells and T cells.

机构信息

Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Korea.

Mirae Cell Bio Co., Ltd., Seoul, 04795, Korea.

出版信息

Sci Rep. 2023 Dec 20;13(1):22694. doi: 10.1038/s41598-023-50258-2.

Abstract

Contact urticaria (CU) is an inflammatory skin disorder triggered by specific substances upon skin contact, leading to immediate acute or chronic manifestations characterized by swelling and redness. While mesenchymal stem cells (MSCs) are increasingly recognized for their therapeutic potential in immune diseases, research on the efficacy and mechanisms of stem cell therapy for urticaria remains scarce. This study investigates the regulatory role of embryonic-stem-cell-derived multipotent MSCs (M-MSCs) administered in a CU mouse model. Therapeutic effects of M-MSC administration were assessed in a Trimellitic anhydride-induced contact urticaria model, revealing significant inhibition of urticarial reactions, including ear swelling, itchiness, and skin lesion. Moreover, M-MSC administration exerted control over effector T cell activities in major lymphoid and peripheral tissues, while also suppressing mast cell degranulation in peripheral tissues. Notably, the inhibitory effects mediated by M-MSCs were found to be TGF-β-dependent. Our study demonstrates the capacity of M-MSCs to regulate contact urticaria in a murine model, harmonizing the activation of inflammatory T cells and mast cells. Additionally, we suggest that TGF-β derived from M-MSCs could play a pivotal role as an inhibitory mechanism in contact urticaria.

摘要

接触性荨麻疹(CU)是一种炎症性皮肤病,由皮肤接触特定物质触发,导致立即出现急性或慢性表现,表现为肿胀和发红。间充质干细胞(MSCs)因其在免疫疾病中的治疗潜力而越来越受到关注,但关于干细胞治疗荨麻疹的疗效和机制的研究仍然很少。本研究调查了胚胎干细胞衍生的多能间充质干细胞(M-MSCs)在 CU 小鼠模型中的调节作用。在三甲基戊二酸酐诱导的接触性荨麻疹模型中评估了 M-MSC 给药的治疗效果,结果显示对荨麻疹反应(包括耳肿胀、瘙痒和皮肤损伤)有显著抑制作用。此外,M-MSC 给药还控制了主要淋巴和外周组织中效应 T 细胞的活性,同时抑制了外周组织中肥大细胞的脱颗粒。值得注意的是,M-MSCs 介导的抑制作用依赖于 TGF-β。我们的研究表明 M-MSCs 能够调节小鼠模型中的接触性荨麻疹,协调炎症性 T 细胞和肥大细胞的激活。此外,我们认为 M-MSCs 衍生的 TGF-β可能作为接触性荨麻疹的一种抑制机制发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc9b/10733409/fd80a4ee52dd/41598_2023_50258_Fig1_HTML.jpg

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