title: Jagged-2 enhances immunomodulatory activity in adipose derived mesenchymal stem cells.
abstract: Adipose derived Mesenchymal stem cells (AMSCs) are able to expand in vitro and undergo differentiation into multiple cell lineages, yet have low immunogenicity while exhibiting several immunoregulatory characteristics. We sought to investigate the immunomodulatory mechanisms of AMSCs to better understand their immunogenic properties. Following 10 days of chondrogenic differentiation or 48 hours of IFN-γ pretreatment, AMSCs retained low level immunogenicity but prominent immunoregulatory activity and AMSC immunogenicity was enhanced by chondrogenic differentiation or IFN-γ treatment. We found Jagged-2 expression was significantly elevated following chondrogenic differentiation or IFN-γ pretreatment. Jagged-2-RNA interference experiments suggested that Jagged-2-siRNA2 suppresses Jagged-2 expression during chondrogenic differentiation and in IFN-γ pretreated AMSCs. Besides, Jagged-2 interference attenuated immunosuppressive activity by mixed lymphocyte culture and mitogen stimulation experiments. So, the immunoregulatory activity of AMSCs, to some extent dependent upon Jagged-2, might be stronger after multilineage differentiation or influence from inflammatory factors. This may also be why rejection does not occur after allogeneic AMSCs differentiate into committed cells.
authors.affiliation: The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Xishan
authors.affiliation: Institute of Basic medicine. Peking Union Medical College, Chinese Academy of Medical Science, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Bin
authors.affiliation: Clinical department, Capital Medical University.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Haiyue
authors.affiliation: The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Xiaowei
authors.affiliation: The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Bai
authors.initials: B
authors.lastname: Jingwen
authors.affiliation: The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Guojun
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D020219:Chondrogenesis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology; D000072101:Jagged-2 Protein; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D007371:Interferon-gamma