CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus 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...
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| Format: | Article |
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/34485/ |
| _version_ | 1848794865520869376 |
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| author | Poissonnier, Amanda Sanseau, 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, Cecile Ducret, Thomas Vacher, Anne-Marie Barrow, Paul A. Flynn, Robin J. Vacher, Pierre Legembre, Patrick |
| author_facet | Poissonnier, Amanda Sanseau, 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, Cecile 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 may be attractive therapeutic approach for SLE treatment. |
| first_indexed | 2025-11-14T19:22:59Z |
| format | Article |
| id | nottingham-34485 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:22:59Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-344852020-05-04T17:52:30Z https://eprints.nottingham.ac.uk/34485/ CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice Poissonnier, Amanda Sanseau, 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, Cecile 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 may be attractive therapeutic approach for SLE treatment. Elsevier 2016-05-10 Article PeerReviewed Poissonnier, Amanda, Sanseau, 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, Cecile, Ducret, Thomas, Vacher, Anne-Marie, Barrow, Paul A., Flynn, Robin J., Vacher, Pierre and Legembre, Patrick (2016) CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice. Immunity . ISSN 1097-4180 (In Press) Calcium; CD95; Inflammation; Lupus; Sphingosine-1 phosphate; Th17 cell |
| spellingShingle | Calcium; CD95; Inflammation; Lupus; Sphingosine-1 phosphate; Th17 cell Poissonnier, Amanda Sanseau, 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, Cecile Ducret, Thomas Vacher, Anne-Marie Barrow, Paul A. Flynn, Robin J. Vacher, Pierre Legembre, Patrick CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice |
| title | CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice |
| title_full | CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice |
| title_fullStr | CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice |
| title_full_unstemmed | CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice |
| title_short | CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice |
| title_sort | cd95 recruits plcγ1 to trigger a calcium response promoting th17 accumulation in inflamed organs of lupus mice |
| topic | Calcium; CD95; Inflammation; Lupus; Sphingosine-1 phosphate; Th17 cell |
| url | https://eprints.nottingham.ac.uk/34485/ |