Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, No. 155, Section 2, Li-Nong Street, Taipei 11221, Taiwan ; The Genomics Research Center, Academia Sinica, Taipei 11574, Taiwan ; Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11574, Taiwan.
Evid Based Complement Alternat Med. 2013;2013:513542. doi: 10.1155/2013/513542. Epub 2013 Jun 24.
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.
LZ-8 是一种从灵芝（又称灵芝或灵芝）中分离出来的免疫调节蛋白，已被证明可促进 T 细胞的细胞增殖和 IL-2 产生。在这项研究中，我们表明 LZ-8 诱导小鼠和人 CD4(+) T 细胞扩增为 FOXP3(+)调节性 T (Treg) 细胞。LZ-8 处理分别刺激了小鼠和人原发性 CD4(+) T 细胞 Treg 群体的 4 倍和 10 倍扩增。此外，在 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 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 依赖性诱导的 IL-2 参与 Treg 形成和 IL-10 产生。通过 DSS 诱导的结肠炎小鼠模型证实了 LZ-8 的抑制活性；通过过继转移 LZ-8 处理的 CD4(+) T 细胞缓解了疾病。总之，鉴定了 LZ-8 的新调节功能，并阐明了该功能的分子机制。
