title: Interferon-γ regulates the function of mesenchymal stem cells from oral lichen planus via indoleamine 2,3-dioxygenase activity.
abstract: BACKGROUND
  Little is known about mesenchymal stem cells (MSCs) in normal or inflammatory oral mucosal tissues, such as in oral lichen planus (OLP). Our objectives were to identify, isolate, and characterize MSCs from normal human oral mucosa and OLP lesions, and to evaluate indoleamine 2,3 dioxygenase (IDO) activity in mediating immunomodulation of MSCs from these tissues.
  
  
  METHODS
  Expressions of MSCs-related markers were examined in isolated cells by flow cytometry. Self-renewal and multilineage differentiations were studied to characterize these MSCs. Interferon-γ (IFN-γ), IDO, and STRO-1 were assessed by immunofluorescence. MSCs from oral mucosa and OLP or IFN-γ-pretreated MSCs were co-cultured with allogeneic mixed lymphocyte reaction assays (MLR). Proliferation and apoptosis of MLR or MSCs were detected by CCK8 and the annexin V-FITC apoptosis detection kit, respectively. IDO expression and activity were measured by real-time PCR, Western blotting, and high-performance liquid chromatography.
  
  
  RESULTS
  Isolated cells from oral mucosa and OLP expressed MSC-related markers STRO-1, CD105, and CD90 but were absent for hematopoietic stem cell markers CD34. Besides, they all showed self-renewal and multilineage differentiation capacities. MSCs in OLP presented STRO-1/IDO+ phenotype by immunofluorescence. MSCs and IFN-γ-pretreated MSCs could inhibit lymphocyte proliferation via IDO activity, but not via cell apoptosis. Long-term IFN-γ could also inhibit MSC proliferation via IDO activity.
  
  
  CONCLUSIONS
  Mesenchymal stem cells can be isolated from human oral mucosa and OLP tissues. Besides self-renewal and multilineage differentiation properties, these cells may participate in immunomodulation mediated by IFN-γ via IDO activity in human OLP.
authors.affiliation: School and Hospital of Stomatology, Peking University, Beijing, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Jiangyuan
authors.initials: J
authors.lastname: Song
authors.forename: Ruxi
authors.initials: R
authors.lastname: Luo
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Dongdong
authors.initials: D
authors.lastname: Mu
authors.forename: Sha
authors.initials: S
authors.lastname: Su
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ji
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Ren
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation; D000066673:Cell Self Renewal / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D000071063:Endoglin; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D017676:Lichen Planus, Oral / Q000201:enzymology / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000201:enzymology / Q000502:physiology*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology; D039902:Multipotent Stem Cells / Q000502:physiology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology; D018800:Thy-1 Antigens / Q000032:analysis
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C064206:ENG protein, human; D000071063:Endoglin; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011956:Receptors, Cell Surface; C525591:STRO-1 antigen, human; D018800:Thy-1 Antigens; D007371:Interferon-gamma
keywords: indoleamine 2,3-dioxygenase; interferon-γ; mesenchymal stem cells; oral lichen planus