title: Berberine suppresses Th17 and dendritic cell responses.
abstract: OBJECTIVE
  Berberine (BBR) has been shown to exert immunosuppressive and anti-inflammatory effects in several autoimmune diseases. This study was designed to investigate the possible effect of BBR on Th17 and dendritic cell (DC) responses.
  
  
  METHODS
  Twelve patients with active VKH disease and 20 healthy individuals were enrolled in this study. CD4(+) T cells and CD14(+) monocytes were isolated from peripheral blood mononuclear cells using magnetic-activated cell sorting. Monocyte-derived DCs were generated by culturing monocytes with GM-CSF and IL-4. Proinflammatory cytokines secreted by CD4(+) T cells and LPS induced DCs when exposed to BBR or only vehicle were detected by ELISA. The frequency of IL-17-producing CD4(+) T cells and the surface markers of BBR-treated DCs were measured by flow cytometry.
  
  
  RESULTS
  Activation of CD4(+) T cells using anti-CD3 and anti-CD28 showed a higher Th17 response in active VKH patients. BBR showed a direct suppression of the Th17 response both in active VKH patients and healthy donors. It also suppressed the Th17 response indirectly by influencing DC maturation. On the one hand, BBR downregulated the expression of costimulatory molecules (CD40, CD80, and CD86) and, on the other hand, it inhibited IL-6, IL-1β, and IL-23 secretion by DCs.
  
  
  CONCLUSIONS
  These findings suggest that the inhibitory effect of BBR on the Th17 response was mediated by a direct action on T cells as well as an indirect effect via DCs. This study provides new evidence that the natural compound BBR is of great value in the search for novel therapeutic agents in the treatment of T-cell-mediated autoimmune diseases.
authors.affiliation: First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hongsong
authors.initials: H
authors.lastname: Yu
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002470:Cell Survival; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism; D014607:Uveomeningoencephalitic Syndrome / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D001599:Berberine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor