Document Detail


Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway.
MedLine Citation:
PMID:  23028899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MSC display potent suppressive properties initially described a decade ago. More recently, MSC suppressive activities on T-cell effector pathways have been investigated. MSC modulate CD4 differentiation through different mechanisms depending on culture conditions and display disparate activities on T cells according to their differentiation status. A significant amount of evidence for MSC effects on Th17 cells revealed that MSC could be suppressive under diverse circumstances but also enhance Th17 cell activity under other conditions. In the present study, we investigated the suppressive effects of MSC on Th1 and Th17 subsets of T cells using T cells undergoing Th1 and Th17 polarization or mature Th1 and Th17 cells. MSC inhibited the proliferation of T cells during their differentiation toward Th1 cells and mature Th1 cells. This suppressive effect was maintained in a transwell cell culture insert demonstrating the major role played by soluble factors. Using the transwell cell separation barrier, we observed that MSC decrease the number of T cells undergoing Th17 differentiation whereas they did not affect IL-17 production by mature Th17, demonstrating the need for cell contact for suppressing Th17 cell function. Moreover, we reported that PD-L1 is highly expressed on MSC co-cultured with differentiating or polarized Th1 and Th17 cells. Using neutralizing antibodies specific for PD-L1 and PD-1 we showed that the mechanisms by which MSC mediate Th17 cell repolarization depend on PD-L1 expression on MSC. Taken together our results demonstrated a cell-to-cell contact depend mechanism in the selective immunosuppression of MSC on mature Th17 cells through up-regulation of PD-L1.
Authors:
Patricia Luz-Crawford; Danièle Noël; Ximena Fernandez; Maroun Khoury; Fernando Figueroa; Flavio Carrión; Christian Jorgensen; Farida Djouad
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-17
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45272     Citation Subset:  IM    
Affiliation:
Inserm, U 844, Montpellier, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Neutralizing / pharmacology
Antigens, CD274 / antagonists & inhibitors,  genetics*,  metabolism
Cell Communication / genetics
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Diffusion Chambers, Culture
Gene Expression Regulation / drug effects
Interleukin-17 / biosynthesis
Mesenchymal Stromal Cells / cytology,  metabolism*
Mice
Programmed Cell Death 1 Receptor / antagonists & inhibitors,  genetics*,  metabolism
Signal Transduction / drug effects,  genetics*
Th1 Cells / cytology,  metabolism*
Th17 Cells / cytology,  metabolism*
Chemical
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/Antigens, CD274; 0/Cd274 protein, mouse; 0/Interleukin-17; 0/Pdcd1 protein, mouse; 0/Programmed Cell Death 1 Receptor
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