title: Trametes versicolor protein YZP activates regulatory B lymphocytes - gene identification through de novo assembly and function analysis in a murine acute colitis model.
abstract: BACKGROUND
  Trametes versicolor (Yun-Zhi) is a medicinal fungus used as a chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies of T. versicolor extracts have been documented, the active ingredients and mechanisms underlying the actions of these extracts remain uncharacterized.
  
  
  RESULTS
  We purified a new protein, YZP, from the fruiting bodies of T. versicolor and identified the gene encoding YZP using RNA-seq and de novo assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide. YZP induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP specifically triggered the differentiation of CD1d(+) B cells into IL-10-producing regulatory B cells (Bregs) and enhanced the expression of CD1d. YZP-induced B cells suppressed approximately 40% of the LPS-activated macrophage production of inflammatory cytokines in a mixed leukocyte reaction and significantly alleviated the disease activity and colonic inflammation in a DSS-induced acute colitis murine model. Furthermore, YZP activated Breg function via interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling pathway.
  
  
  CONCLUSIONS
  We purified a novel Breg-stimulating protein, YZP, from T. versicolor and developed an advanced approach combining RNA-seq and de novo assembly technologies.to clone its gene. We demonstrated that YZP activated CD1d(+) Breg differentiation through TLR2/4-mediated signaling pathway, and the YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in murine acute colitis models.
authors.affiliation: Center for Biotechnology, National Taiwan University, Taipei, Taiwan ; Department of Horticulture, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Chou
authors.initials: YC
authors.lastname: Kuan
authors.forename: Ying-Jou
authors.initials: YJ
authors.lastname: Wu
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Hung
authors.forename: Fuu
authors.initials: F
authors.lastname: Sheu
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D001483:Base Sequence; D003092:Colitis / Q000235:genetics / Q000276:immunology*; D004271:DNA, Fungal; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal; D051379:Mice; D008969:Molecular Sequence Data; D055454:Trametes / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins
references.citation: J Clin Invest. 1998 Jan 15;101(2):311-20
references.pmid: 9435302
references.citation: J Immunol. 2007 Jun 15;178(12):7779-86
references.pmid: 17548615
references.citation: Am J Pathol. 2011 Feb;178(2):735-43
references.pmid: 21281806
references.citation: Inflamm Bowel Dis. 2009 Mar;15(3):341-52
references.pmid: 18942757
references.citation: Nat Rev Genet. 2010 Jan;11(1):31-46
references.pmid: 19997069
references.citation: J Exp Med. 1997 Nov 17;186(10):1749-56
references.pmid: 9362534
references.citation: PLoS One. 2007 Sep 12;2(9):e863
references.pmid: 17848994
references.citation: Phytother Res. 2011 Aug;25(8):1257-61
references.pmid: 21796702
references.citation: PLoS One. 2011;6(6):e21004
references.pmid: 21698210
references.citation: Nat Rev Genet. 2011 Sep 07;12(10):671-82
references.pmid: 21897427
references.citation: J Med Food. 2006 Summer;9(2):175-81
references.pmid: 16822202
references.citation: J Leukoc Biol. 2009 Oct;86(4):877-89
references.pmid: 19498044
references.citation: Autoimmun Rev. 2012 Jul;11(9):670-7
references.pmid: 22155204
references.citation: Immunity. 2002 Feb;16(2):219-30
references.pmid: 11869683
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13938-43
references.pmid: 10570177
references.citation: Int Immunopharmacol. 2010 Feb;10(2):239-46
references.pmid: 19909827
references.citation: Biomed Pharmacother. 2009 Jul;63(6):409-12
references.pmid: 18848763
references.citation: Carbohydr Polym. 2012 Nov 6;90(4):1395-410
references.pmid: 22944395
references.citation: Anticancer Res. 1991 Mar-Apr;11(2):993-9
references.pmid: 2064356
references.citation: J Immunol. 2012 Feb 1;188(3):1036-48
references.pmid: 22198952
references.citation: Nat Rev Immunol. 2010 Apr;10(4):236-47
references.pmid: 20224569
references.citation: Nat Rev Rheumatol. 2010 Nov;6(11):636-43
references.pmid: 20856268
references.citation: Life Sci. 1999;64(12):1005-11
references.pmid: 10210283
references.citation: Cancer Epidemiol Biomarkers Prev. 1995 Apr-May;4(3):275-81
references.pmid: 7606203
references.citation: Nat Clin Pract Rheumatol. 2008 Dec;4(12):657-66
references.pmid: 19037227
references.citation: Nat Biotechnol. 2008 Oct;26(10):1135-45
references.pmid: 18846087
references.citation: J Agric Food Chem. 2009 Jul 22;57(14):6129-39
references.pmid: 19548679
references.citation: J Immunol. 2000 Nov 1;165(9):4848-53
references.pmid: 11046008
references.citation: Respir Med. 2003 Jun;97(6):618-24
references.pmid: 12814145
references.citation: Nature. 2010 Jan 21;463(7279):311-7
references.pmid: 20010809
references.citation: Eur J Immunol. 2007 Nov;37(11):3040-53
references.pmid: 17918201
references.citation: J Immunol. 2009 Jun 15;182(12):7459-72
references.pmid: 19494269
references.citation: J Agric Food Chem. 2010 Aug 11;58(15):8535-44
references.pmid: 20681640
references.citation: Int J Biochem Cell Biol. 1996 May;28(5):601-7
references.pmid: 8697105
references.citation: J Immunol. 1991 Dec 1;147(11):3815-22
references.pmid: 1940369
references.citation: Int Immunopharmacol. 2012 Sep;14(1):114-20
references.pmid: 22749731
references.citation: PLoS One. 2012;7(7):e41901
references.pmid: 22848651
references.citation: J Biol Chem. 2006 Aug 25;281(34):24111-23
references.pmid: 16798741
references.citation: Biotechnol Adv. 2003 Apr;21(2):109-22
references.pmid: 14499133
references.citation: PLoS One. 2012;7(2):e31560
references.pmid: 22347493
references.citation: J Agric Food Chem. 2009 May 27;57(10):4130-41
references.pmid: 19371137
references.citation: Curr Med Chem. 2000 Jul;7(7):715-29
references.pmid: 10702635
references.citation: Gen Pharmacol. 1998 Jan;30(1):1-4
references.pmid: 9457474
references.citation: J Exp Med. 1999 Oct 4;190(7):995-1004
references.pmid: 10510089
references.citation: Immunol Today. 1997 Sep;18(9):428-32
references.pmid: 9293158
references.citation: RNA. 2010 May;16(5):991-1006
references.pmid: 20360395
references.citation: J Exp Med. 1994 May 1;179(5):1529-37
references.pmid: 8163936
references.citation: J Clin Pharmacol. 2002 Sep;42(9):976-84
references.pmid: 12211223
references.citation: PLoS One. 2012;7(10):e47442
references.pmid: 23071809