title: Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model.
abstract: BACKGROUND
  Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-β1 (TGF-β1) content, PCLs may exert immunosuppressive and anti-inflammatory functions.
  
  
  METHODS
  PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-β in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-β1 was used as control.
  
  
  RESULTS
  PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-β-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-β-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice.
  
  
  CONCLUSIONS
  S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan; Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan; College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Family Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan; Research Department, Human Protein Process Science, Lille, France.
authors.forename: Yueh-Lun
authors.initials: YL
authors.lastname: Lee
authors.forename: Lin-Wen
authors.initials: LW
authors.lastname: Lee
authors.forename: Chen-Yao
authors.initials: CY
authors.lastname: Su
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Yang
authors.forename: Sy-Jye
authors.initials: SJ
authors.lastname: Leu
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Shieh
authors.forename: Thierry
authors.initials: T
authors.lastname: Burnouf
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D001792:Blood Platelets / Q000187:drug effects / Q000821:virology*; D003902:Detergents / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D017713:Platelet Transfusion; D012997:Solvents / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D003902:Detergents; D012997:Solvents