title: Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.
abstract: Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.
authors.affiliation: Joint Immunology Laboratory, Institute of Health Sciences, Shanghai 200025, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Qin
authors.forename: Bingshi T
authors.initials: BT
authors.lastname: Guo
authors.forename: Bing
authors.initials: B
authors.lastname: Wan
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Limin
authors.initials: L
authors.lastname: Lu
authors.forename: Lili
authors.initials: L
authors.lastname: Wu
authors.forename: Ying Qin
authors.initials: YQ
authors.lastname: Zang
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001599:Berberine / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*
chemical_list: D004365:Drugs, Chinese Herbal; D020381:Interleukin-17; D001599:Berberine