Abstract: | |
Following allogeneic hematopoietic stem cell transplantation (HSCT), interferon (IFN)-γ levels in the recipient's body can strongly influence the clinical outcome. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are lucrative as biological tolerance inducers in HSCT settings. Hence, we studied the molecular mechanism of how UC-MSCs influence natural killer (NK) cell-mediated IFN-γ production. Allogeneic NK cells were cultured in direct contact with UC-MSCs or cell free supernatants from MSC cultures (MSC conditioned media). We found that soluble factors secreted by UC-MSCs strongly suppressed IL-12/IL-18-induced IFN-γ production by NK cells by reducing phosphorylation of STAT4, NF-κB as well as T-bet activity. UC-MSCs secreted considerable amounts of Activin-A, which could suppress IFN-γ production by NK cells. Neutralisation of Activin-A in MSC conditioned media significantly abrogated their suppressive abilities. Till date, multiple groups have reported that prostaglandin (PG)-E2 produced by MSCs can suppress NK cell functions. Indeed, we found that inhibition of PGE2 production by MSCs could also significantly restore IFN-γ production. However, the effects of Activin-A and PGE2 were not cumulative. To the best of our knowledge, we are first to report the role of Activin-A in MSC mediated suppression of IFN-γ production by NK cells.
|
|
License of this version: | CC BY 4.0 Unported - http://creativecommons.org/licenses/by/4.0/ |
Publication type: | Article |
Publishing status: | publishedVersion |
Publication date: | 2014 |
Keywords english: | Activin-A, IFN-γ production, NK cell, Suppression, T-bet, UC-MSC, 5' nucleotidase, activin A, CD14 antigen, CD19 antigen, CD34 antigen, CD45 antigen, endoglin, gamma interferon, HLA DR antigen, immunoglobulin enhancer binding protein, indometacin, interleukin 12, interleukin 18, prostaglandin E2, STAT4 protein, Thy 1 antigen, transcription factor RelA, transcription factor T bet, adipogenesis, Article, bone development, cell differentiation, chondrogenesis, DNA binding, down regulation, enzyme linked immunosorbent assay, flow cytometry, fluorescence activated cell sorting, human, human cell, infant, mesenchymal stem cell, natural killer cell, peripheral blood mononuclear cell, protein expression, protein phosphorylation, umbilical cord derived mesenchymal stem cell |
DDC: | 610 | Medizin, Gesundheit |
Showing items related by title, author, creator and subject.