A New Protein YZ-1 Isolated from Coriolus versicolor Activates Regulatory B cell Differentiation - Mechanism and Application on Inflammatory Bowel Disease

• Main Authors: Yen-Chou Kuan, 官彥州
• Other Authors: Fuu Sheu
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/87976839472069452716

碩士 === 國立臺灣大學 === 園藝學研究所 === 100 === Coriolus versicolor is a medicinal fungus appreciated as a folk remedy worldwide. The polysaccharopeptide extracts of C. versicolor were considered the main anti-tumor and immune-potentiating agents; however, the polysaccharopeptides were mixtures of multiple constituents containing 28±10% proteins. The aim of this study was to isolate an immunomodulatory protein from C. versicolor and to assess its function. Through ion-exchange chromatography, a 14 kDa non-glycosylated protein was purified and named as YZ-1. The stimulating effect of YZ-1 on MACS-purified murine splenic CD19+ B cells was evaluated by flow cytometry, qPCR, and ELISA. YZ-1 activated B cell proliferation and differentiated B cells into IgM-secreting CD138+ plasma cells as well as IL-10-secreting CD1d+ regulatory B cells (Bregs). Furthermore, YZ-1-induced B cells (BYZ-1) inhibited TNF-α and IL-1β production by LPS-activated mice peritoneal macrophages in vitro. In a DSS-induced colitis murine model, adoptive transfer of BYZ-1 significantly reduced the disease activity, alleviated intestinal injuries, and suppressed colonic inflammatory cytokine expression. Blockage of toll like receptor (TLR) 4 and TLR2 by neutralizing antibodies limited YZ-1-induced B cell activation. In addition, the binding between YZ-1 and B cells was impaired in TLR4-/- and TLR2-/- mice. The expression of MYD88, TIRAP, TRAF6, NF-κB, and Prdm1 were induced in BYZ-1, suggesting that these cells were activated through a TLR-mediated signaling pathway. In conclusion, YZ-1 was a new protein purified from C. versicolor that could activate plasmacytic and Breg differentiation via a TLR4/TLR2-dependent mechanism. Moreover, BYZ-1 had immune-suppressive potential and showed efficacies in a cell-base immunotherapy against autoimmune disease. These findings provided insights to the study of C. versicolor regarding its active ingredient and immune-regulatory function.