Recombinant LZ-8-induced CD4+CD25+T Cells in Cytokines Expression and Immunomodulatory Function

• Main Authors: Li-Juan Ma, 馬儷娟
• Other Authors: Hsien-Yeh Hsu
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/5ph4pf

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 97 === Ganoderma lucidum (G. lucidum, Ling-Zhi, 靈芝) has been used as a medicine in Asia for years to treat numerous human diseases. An immunomodulatory protein named Ling Zhi-8 (LZ-8) existing in the mycelia of G. lucidum has been cloned and expressed as a recombinant protein rLZ-8. Previous results indicated that rLZ-8 enhanced IL-2, IFN-γ secretion and up-regulation of CD25 on surface of T cells in vitro. It has been reported that rLZ-8 is able to suppress autoimmune diabetes in mice. Herein we tested the hypothesis of rLZ-8 exerting immunomodulatory capacities. First, we demonstrated that rLZ-8 induced cytokines production including IL-2, IFN-γ and IL-10 in human primary CD4+ T cells. Also, we found that the rLZ-8 induced IL-2 plays an important role in IL-10 production. In addition, rLZ-8 promoted Naïve CD4+ T cells into induced-CD4+CD25+ regulatory T cells (Tregs) and the suppressive activity in vitro. To investigate the mechanism by which rLZ-8 induction of Tregs, we found that rLZ-8-induced Tregs differentiation via a CD45-dependent pathway. Moreover, since Tregs play important roles in the prevention of autoimmune disease, we further tested the role of rLZ-8-induced Tregs in dextrane sulfate sodium (DSS)-proned colitis, one kind of autoimmune inflammatory bowel diseases. We evidenced that ex vivo-generated rLZ-8-induced CD4+ T cells (~40% Tregs) injected into colitis-like mice, and found the colitis symptom was largely reduced as compared to the control mice. In conclusion, we demonstrate that rLZ-8 has immunomodulatory function through induced cytokines production and regulatory T cells differentiation in vitro, as well as that rLZ-8 induced-Tregs could reduce inflammation of colitis-like mice model in vivo. Our current results suggest rLZ-8 has potential as an immunomodulatory agent.