title: Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.
abstract: Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression.
authors.affiliation: Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; Noncommunicable Diseases Research Centre, Fasa University of Medical Sciences, Fasa, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Moravej
authors.affiliation: Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
authors.affiliation: Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Amir-Hassan
authors.initials: AH
authors.lastname: Zarnani
authors.affiliation: Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Yaghobi
authors.affiliation: Professor 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: Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khosravi
authors.affiliation: Noncommunicable Diseases Research Centre, Fasa University of Medical Sciences, Fasa, Iran.
authors.forename: Amin
authors.initials: A
authors.lastname: Kouhpayeh
authors.affiliation: Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: Karimimh@sums.ac.ir.
authors.forename: Mohammad-Hossein
authors.initials: MH
authors.lastname: Karimi
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics*; D015415:Biomarkers; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006085:Graft Survival; D056747:Immunomodulation; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
keywords: IDO; Immunomodulation; MSCs; PD-L1; Transplantation