title: Mesenchymal Stem Cells Upregulate the Expression of PD-L1 But Not VDR in Dendritic Cells.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) show immunomodulatory functions. But the exact mechanism underlying these activities of MSCs is still not completely understood. There have been a few studies which have assessed the effects of these cells on dendritic cells (DCs) function. Given the importance of programmed cell death receptor-1 (PD-L1) and vitamin D receptor (VDR) expression in induction of tolerance in DCs, we were encouraged to investigate if one of the immunomodulatory functions of MSCs could be inducing upregulation of PD-L1 and VDR on DCs or not.
  
  
  METHODS
  DCs were co-cultured with MSCs or treated with them in transwell plates in the presence or absence of Lipopolysaccharide (LPS). Expression of PD-L1 and VDR mRNA and proteins in treated DCs were assessed by Real-time PCR and Western blot techniques. Furthermore, treated DCs were co-cultured with allogeneic T-cells, and T-cell proliferation and cytokine secretions in co-culture supernatants were assessed.
  
  
  RESULTS
  The results showed that PD-L1 but not VDR expression is significantly upregulated in the DCs co-cultured with MSCs. Furthermore, cell-to-cell contact and also presence of maturation inducers like LPS is necessary for this function. Moreover, our results indicated that MSCs could induce tolerogenic DCs (TolDCs) which could decrease the secretion of IL-2 by T-cells and inhibit T-cell proliferation as well as increase secretion of IL-10.
  
  
  CONCLUSIONS
  Overall, our results show that MSCs may have several suppressive effects on immune responses by induction of TolDCs expressing more PD-L1 immunomodulatory molecule and change the cytokines profile of DCs and T-cells.
authors.affiliation: a Transplant Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.|b Noncommunicable Diseases Research Centre , Fasa University of Medical Sciences , Fasa , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Moravej
authors.affiliation: a Transplant Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Mohammad-Hossein
authors.initials: MH
authors.lastname: Karimi
authors.affiliation: a Transplant Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
authors.affiliation: a Transplant Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.affiliation: c Nanobiotechnology Research Center , Avicenna Research Institute, ACECR , Tehran , Iran.|d Immunology Research Center , Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Amir-Hasan
authors.initials: AH
authors.lastname: Zarnani
authors.affiliation: a Transplant Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Yaghobi
authors.affiliation: a Transplant Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khosravi
authors.affiliation: e Alborzi Clinical Microbiology Research Center, Nemazee Hospital , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kalani
authors.affiliation: f Department of Immunology, School of Medicine , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Gharesi-Fard
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000502:physiology*; D007108:Immune Tolerance; D056747:Immunomodulation; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007376:Interleukin-2; D007519:Isoantigens; D018167:Receptors, Calcitriol; D016753:Interleukin-10
keywords: DCs; MSCs; PD-L1; VDR; immunomodulation