Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity
Creators: name: Chatterjee, Debanjana
name: Marquardt, Nicole
name: Tufa, Dejene Milkessa
name: Beauclair, Guillaume
name: Low, Hui Zhi
name: Hatlapatka, Tim
name: Hass, Ralf
name: Kasper, Cornelia
name: Kaisenberg, Constantin Von
name: Schmidt, Reinhold Ernst
name: Jacobs, Roland
Publisher: name: London : BioMed Central Ltd.
Year: 2014
Subjects: subject: Gamma-secretase
subject: IL-1β
subject: Immunosuppression
subject: NK cell cytotoxicity
subject: UC-MSC
subject: 5' nucleotidase
subject: CD14 antigen
subject: CD16 antigen
subject: CD19 antigen
subject: CD27 antigen
subject: CD45 antigen
subject: CD69 antigen
subject: CD94 antigen
subject: cyclooxygenase 2
subject: endoglin
subject: gamma secretase
subject: HLA DR antigen
subject: interleukin 1 receptor
subject: interleukin 1beta
subject: Janus kinase
subject: killer cell immunoglobulin like receptor
subject: kynurenine
subject: L selectin
subject: lysosome associated membrane protein 1
subject: natural killer cell receptor NKG2A
subject: natural killer cell receptor NKG2D
subject: presenilin
subject: prostaglandin E2
subject: Thy 1 antigen
subject: antigen expression
subject: Article
subject: blood sampling
subject: cell culture
subject: cell differentiation
subject: cell function
subject: cell interaction
subject: coculture
subject: controlled study
subject: degranulation
subject: enzyme activation
subject: enzyme activity
subject: enzyme linked immunosorbent assay
subject: enzyme phosphorylation
subject: flow cytometry
subject: human
subject: human cell
subject: immunostimulation
subject: mesenchymal stem cell
subject: molecular interaction
subject: natural killer cell mediated cytotoxicity
subject: normal human
subject: peripheral blood mononuclear cell
subject: phenotype
subject: prostaglandin release
subject: protein degradation
subject: protein function
subject: signal transduction
subject: umbilical cord
subject: upregulation
subject: Dewey Decimal Classification::500 | Naturwissenschaften
subject: Dewey Decimal Classification::500 | Naturwissenschaften::570 | Biowissenschaften, Biologie

description: Background: Mesenchymal stem cells (MSCs) are increasingly considered to be used as biological immunosuppressants in hematopoietic stem cell transplantation (HSCT). In the early reconstitution phase following HSCT, natural killer (NK) cells represent the major lymphocyte population in peripheral blood and display graft-vs-leukemia (GvL) effects. The functional interactions between NK cells and MSCs have the potential to influence the leukemia relapse rate after HSCT. Until date, MSC-NK cell interaction studies are largely focussed on bone marrow derived (BM)-MSCs. Umbilical cord derived (UC)-MSCs might be an alternative source of therapeutic MSCs. Thus, we studied the interaction of UC-MSCs with unstimulated allogeneic NK cells.Results: UC-MSCs could potently suppress NK cell cytotoxicity in overnight cultures via soluble factors. The main soluble immunosuppressant was identified as prostaglandin (PG)-E2. Maximal PGE2 release involved IL-1β priming of MSCs after close contact between the NK cells and UC-MSCs. Interestingly, blocking gamma-secretase activation alleviated the immunosuppression by controlling PGE2 production. IL-1 receptor activation and subsequent downstream signalling events were found to require gamma-secretase activity.Conclusion: Although the role of PGE2 in NK cell-MSC has been reported, the requirement of cell-cell contact for PGE2 induced immunosuppression remained unexplained. Our findings shed light on this puzzling observation and identify new players in the NK cell-MSC crosstalk.