Reishi Protein LZ-8 Induces FOXP3(+) Treg Expansion via a CD45-Dependent Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice.

Reishi Protein LZ-8 Induces FOXP3(+) Treg Expansion via a CD45-Dependent Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice.
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Reishi蛋白LZ-8通过CD45依赖性信号通路诱导Foxp3(+)Treg膨胀,并减轻小鼠的急性肠炎。

DOI:
10.1155/2013/513542
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发表时间:
2013
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Sheu F
Sheu F
中科院分区:
其他
文献类型:
--
作者:
Hsu HY;Kuan YC;Lin TY;Tsao SM;Hsu J;Ma LJ;Sheu F

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LZ-8 是一种从灵芝(也称为灵芝或灵芝)中分离出来的免疫调节蛋白,已被证明可以促进 T 细胞的细胞增殖和 IL-2 的产生。在这项研究中,我们证明 LZ-8 诱导小鼠和人类 CD4+ T 细胞扩增为 FOXP3+ 调节性 T (Treg) 细胞。研究发现,LZ-8 治疗可刺激小鼠和人类原代 CD4+ T 细胞的 Treg 群体分别扩增 4 倍和 10 倍。此外,LZ-8处理的CD4+T细胞中诱导了CTLA-4和IL-10的表达。使用中和抗体和基因缺陷的 T 细胞系,我们还发现 LZ-8 通过 CD45 介导的信号通路促进 Treg 扩增,并且 CD18 依赖性的 IL-2 诱导参与 Treg 形成和 IL-10 产生。 LZ-8 的抑制活性通过 DSS 诱导的结肠炎小鼠模型得到证实;通过 LZ-8 处理的 CD4+ T 细胞的过继转移,该疾病得到缓解。总之,确定了 LZ-8 的新调节功能,并阐明了该功能背后的分子机制。
LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as Ling-Zhi or Reishi), has been shown to promote cell proliferation and IL-2 production in T cells. In this study, we show that LZ-8 induces the expansion of both murine and human CD4+ T cells into FOXP3+ regulatory T (Treg) cells. LZ-8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg populations of murine and human primary CD4+ T cells, respectively. In addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4+ T cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway and that the CD18-dependent induction of IL-2 was involved in Treg formation and IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine model of DSS-induced colitis; the disease was alleviated by the adoptive transfer of LZ-8-treated CD4+ T cells. In conclusion, a new regulatory function for LZ-8 was identified, and the molecular mechanisms underlying this function were elucidated.
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