Human umbilical cord-derived mesenchymal stem cells utilise activin-A to suppress interferon-gamma production by natural killer cells

Debanjana Chatterjee, Nicole Marquardt, Dejene Milkessa Tufa, Tim Hatlapatka, Ralf Hass, Cornelia Kasper, Constantin von Kaisenberg, Reinhold Ernst Schmidt, Roland Jacobs

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Article number662
JournalFrontiers in immunology
Volume5
Issue numberDEC
DOIs
StatePublished - 2014

Bibliographical note

Publisher Copyright:
© 2014 Chaterjee, Marquardt, Tufa, Hatlapatka, Hass, Kasper, Von_kaisenberg, Schmidt and Jacobs.

Keywords

  • Activin-A
  • IFN-γ production
  • NK cell
  • Suppression
  • T-bet
  • UC-MSC

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