English, Karen and Barry, Frank P. and Field-Corbett, Ciara and Mahon, Bernard P.
(2007)
IFN-y and TNF-x differentially regulate immunomodulation
by murine mesenchymal stem cells.
Immunology Letters, 110.
pp. 91-100.
ISSN 1879-0542
Abstract
Murine mesenchymal stem cells (MSC) have the ability to inhibit allogeneic immune responses. Two different mechanisms, either cell contactdependent
or independent, have been proposed to account for this immunosuppression. The focus of this study was to elucidate the involvement of
soluble suppressive factors secreted by murine MSC in an inflammatory setting, and their role in MSC immunomodulation. In a non-inflammatory
environment, bone marrow derived murine MSC constitutively expressed low levels of COX-2, PGE-2, TGF-x1 and HGF, but not IL-10, PD-1,
PD-L1 or PD-L2. These MSC were able to significantly reduce alloantigen driven proliferation in mixed lymphocyte reactions as well as mitogen
driven proliferation. The pro-inflammatory cytokines IFN-y and TNF-x did not ablate MSC mediated immunosuppression. MSC expression
of PGE-2, IDO and PD-L1 was differentially regulated by these cytokines. COX-2 and PGE-2 expression by MSC were upregulated by both
IFN-y and TNF-x, and using a biochemical inhibitor this was shown to have an essential, non-redundant role in modulating alloantigen-driven
proliferation. However, the surface expression of PD-L1 was induced by IFN-y but not TNF-x and similarly functional IDO expression was only
induced by IFN-y stimulation. Blocking studies using neutralising antibodies and biochemical antagonists revealed that while PD-L1 induction
was not essential, IDO expression was a prerequisite for IFN-y mediated MSC immunomodulation. These data demonstrate that murine MSC
expression of immunomodulatory factors dramatically changes in a pro-inflammatory environment and that IFN-y in particular has an important
role in regulating MSC immunomodulatory factor expression.
| Item Type: |
Article
|
| Keywords: |
Mesenchymal stem cell; Immunosuppression; Prostaglandin; IDO; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
6842 |
| Identification Number: |
https://doi.org/10.1016/j.imlet.2007.04.001 |
| Depositing User: |
Karen English
|
| Date Deposited: |
19 Jan 2016 16:36 |
| Journal or Publication Title: |
Immunology Letters |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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