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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mooney, Nuala Charron, Dominique Favier, Benoit Taflin, Cécile Baudhuin, Jeremy Glotz, Denis Savenay, Alain Hemon, Patrice Bensussan, Armand |
| Description | Author Affiliation: Taflin C ( Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche Santé 940, Hôpital Saint Louis, 75010 Paris, France.); |
| Abstract | Organ transplantation represents a unique therapeutic option for irreparable organ dysfunction and rejection of transplants results from a breakdown in operational tolerance. Although endothelial cells (ECs) are the first target in graft rejection following kidney transplantation, their capacity to alloactivate and generate particular T lymphocyte subsets that could intervene in this process remains unknown. By using an experimental model of microvascular endothelium, we demonstrate that, under inflammatory conditions, human ECs induced proliferation of memory CD4(+)CD45RA(-) T cells and selectively amplified proinflammatory Th17 and suppressive CD45RA(-)HLA-DR(+)FoxP3(bright) regulatory CD4(+) T lymphocytes (Tregs). Although HLA-DR expression on resting microvascular ECs was sufficient to induce proliferation of memory CD4(+) T cells, Treg amplification was dependent on the interaction with CD54, highly expressed only under inflammatory conditions. Moreover, expansion of Th17 cells was dependent on IL-6 and STAT-3, and inhibition of either specifically impaired Th17, without altering Treg expansion. Collectively these data reveal that the HLA-DR(+) ECs regulate the local inflammatory allogeneic response, promoting either an IL-6/STAT-3-dependent Th17 response or a contact-CD54-dependent regulatory response according to the cytokine environment. Finally, these data open therapeutic perspectives in human organ transplantation based on targeting the IL-6/STAT-3 pathway and/or promoting CD54 dependent Treg proliferation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endothelial Cells Immunology Metabolism HLA-DR Antigens Inflammation T-Lymphocytes, Regulatory Cytology Th17 Cells Cell Proliferation Enzyme-Linked Immunosorbent Assay Flow Cytometry Intercellular Adhesion Molecule-1 Interleukin-6 Oligonucleotides Genetics Polymerase Chain Reaction STAT3 Transcription Factor Statistics, Nonparametric Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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