CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice
CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/45101/ |
| _version_ | 1848797069222871040 |
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| author | Poissonnier, Amanda Sanséau, Doriane Le Gallo, Matthieu Malleter, Marine Levoin, Nicolas Viel, Roselyne Morere, Lucie Penna, Aubin Blanco, Patrick Dupuy, Alain Poizeau, Florence Fautrel, Alain Seneschal, Julien Jouan, Florence Ritz, Jerome Forcade, Edouard Rioux, Nathalie Contin-Bordes, Cécile Ducret, Thomas Vacher, Anne-Marie Barrow, Paul A. Flynn, Robin J. Vacher, Pierre Legembre, Patrick |
| author_facet | Poissonnier, Amanda Sanséau, Doriane Le Gallo, Matthieu Malleter, Marine Levoin, Nicolas Viel, Roselyne Morere, Lucie Penna, Aubin Blanco, Patrick Dupuy, Alain Poizeau, Florence Fautrel, Alain Seneschal, Julien Jouan, Florence Ritz, Jerome Forcade, Edouard Rioux, Nathalie Contin-Bordes, Cécile Ducret, Thomas Vacher, Anne-Marie Barrow, Paul A. Flynn, Robin J. Vacher, Pierre Legembre, Patrick |
| author_sort | Poissonnier, Amanda |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment. |
| first_indexed | 2025-11-14T19:58:01Z |
| format | Article |
| id | nottingham-45101 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:58:01Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-451012020-05-04T18:00:45Z https://eprints.nottingham.ac.uk/45101/ CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice Poissonnier, Amanda Sanséau, Doriane Le Gallo, Matthieu Malleter, Marine Levoin, Nicolas Viel, Roselyne Morere, Lucie Penna, Aubin Blanco, Patrick Dupuy, Alain Poizeau, Florence Fautrel, Alain Seneschal, Julien Jouan, Florence Ritz, Jerome Forcade, Edouard Rioux, Nathalie Contin-Bordes, Cécile Ducret, Thomas Vacher, Anne-Marie Barrow, Paul A. Flynn, Robin J. Vacher, Pierre Legembre, Patrick CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment. Elsevier 2016-07-19 Article PeerReviewed Poissonnier, Amanda, Sanséau, Doriane, Le Gallo, Matthieu, Malleter, Marine, Levoin, Nicolas, Viel, Roselyne, Morere, Lucie, Penna, Aubin, Blanco, Patrick, Dupuy, Alain, Poizeau, Florence, Fautrel, Alain, Seneschal, Julien, Jouan, Florence, Ritz, Jerome, Forcade, Edouard, Rioux, Nathalie, Contin-Bordes, Cécile, Ducret, Thomas, Vacher, Anne-Marie, Barrow, Paul A., Flynn, Robin J., Vacher, Pierre and Legembre, Patrick (2016) CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice. Immunity, 45 (1). pp. 209-223. ISSN 1074-7613 http://www.sciencedirect.com/science/article/pii/S1074761316302503 doi:10.1016/j.immuni.2016.06.028 doi:10.1016/j.immuni.2016.06.028 |
| spellingShingle | Poissonnier, Amanda Sanséau, Doriane Le Gallo, Matthieu Malleter, Marine Levoin, Nicolas Viel, Roselyne Morere, Lucie Penna, Aubin Blanco, Patrick Dupuy, Alain Poizeau, Florence Fautrel, Alain Seneschal, Julien Jouan, Florence Ritz, Jerome Forcade, Edouard Rioux, Nathalie Contin-Bordes, Cécile Ducret, Thomas Vacher, Anne-Marie Barrow, Paul A. Flynn, Robin J. Vacher, Pierre Legembre, Patrick CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice |
| title | CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice |
| title_full | CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice |
| title_fullStr | CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice |
| title_full_unstemmed | CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice |
| title_short | CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice |
| title_sort | cd95-mediated calcium signaling promotes t helper 17 trafficking to inflamed organs in lupus-prone mice |
| url | https://eprints.nottingham.ac.uk/45101/ https://eprints.nottingham.ac.uk/45101/ https://eprints.nottingham.ac.uk/45101/ |