title: Interleukin-17A- or tumor necrosis factor α-mediated increase in proliferation of T cells cocultured with synovium-derived mesenchymal stem cells in rheumatoid arthritis.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) represent promising applications in rheumatoid arthritis (RA). However, the inflammatory niche in the RA synovium could adversely affect MSC function. This study was designed to investigate biologic and immunologic properties of synovium-derived MSCs (SMSCs) in RA, with particular focus on whether cytokines can mediate increase of proliferation of T cells cocultured with SMSCs in RA.
  
  
  METHODS
  Compared with SMSCs from eight healthy donors (HDs), SMSCs from 22 patients with RA (RAp) were evaluated. The methyl thiazolyl tetrazolium (MTT) assay was used to assess cell-population doubling and viability. Multipotentiality of SMSCs was examined by using appropriate culture conditions. Flow cytometry was used to investigate the marker phenotype of SMSCs. Immunomodulation potential of SMSCs was examined by mixed peripheral blood mononuclear cells (PBMCs) reactions, and then by PBMCs or synovial T cells with or without the addition of inflammatory cytokines (interleukin-17A (IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)) after stimulation with phytohemagglutinin (PHA), respectively.
  
  
  RESULTS
  SMSCs from RA patients (RA-SMSCs) showed normal population doubling, cell viability, multiple differentiation characteristics, and surface markers. In either mixed PBMC reactions or PBMC proliferation stimulated with PHA, RA-SMSCs showed normal immunomodulation function compared with SMSCs from healthy donors (HD-SMSCs). However, the increase in proliferation of T cells was observed when IL-17A and TNF-α were added alone or in combination.
  
  
  CONCLUSIONS
  Our data suggest that the inflammatory niche, especially these cytokines, may increase the proliferation of T cells cocultured with SMSCs in RA.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuanjing
authors.initials: Y
authors.lastname: Ding
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D020381:Interleukin-17; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha