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Cited by 195Mesenchymal stem cell researchT-cell and B-cell ImmunologyHematopoietic Stem Cell Transplantation

Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway

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Luz-Crawford, Patricia, Noël, Danièle, Fernandez, Ximena, Khoury, Maroun, Figueroa, Fernando, Carrión, Flavio, Jorgensen, Christian, Djouad, Farida·2012·PLoS ONE
DOI 10.1371/journal.pone.0045272PMC PMC3444478
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Abstract

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.

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  • PD-1 is known to induce anergy in TH17 cells.

    “This reveals a potential mechanism whereby CCR6 controls pathogenicity of TH17 cells in learned-helplessness because PD-1 is known to induce anergy in TH17 cells (Luz-Crawford et al., 2012).”

    From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Luz-Crawford et al., 2012

    The Discussion says PD-L1 signaling through PD-1 can induce anergy in T cells generally. The Results show that this pathway helps suppress mature Th17-cell proliferation and function, but do not establish that it induces anergy specifically in Th17 cells. (LLM, conf=0.85)

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Authors
Luz-Crawford, P., Noël, D., Fernandez, X., Khoury, M., Figueroa, F., Carrión, F., Jorgensen, C., & Djouad, F.
Affiliations
  • Inserm (FR)
  • Universidad de Los Andes, Chile (CL)
Corresponding author
Djouad, Farida
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-09-17
Volume
7
Issue
9
Pages
e45272
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0045272
PMC
PMC3444478
OpenAlex
W1991996112
Cited by
195
References
5
Citations by year
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FWCI
6.26
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Commission (279174)
  • Agence Nationale de la Recherche (ANR-11-INBS-0005)
  • Institut National de la Santé et de la Recherche Médicale
  • Université de Montpellier
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
mesenchymal stem cells, Th17 cells, Th1 cells, PD-1, PD-L1, immunosuppression, T cell differentiation, cell-cell contact, IL-17, T cell proliferation, soluble factors
MeSH terms
Animals, Cell Communication, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Diffusion Chambers, Culture, Signal Transduction, Th1 Cells, Interleukin-17, Cell Proliferation, Mice, Antibodies, Neutralizing, Th17 Cells, Mesenchymal Stem Cells, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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