Amanda Poissonnier
CD95-Mediated Calcium Signaling Promotes T Helper 17 Trafficking to Inflamed Organs in Lupus-Prone Mice
Poissonnier, Amanda; Sans�au, 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, C�cile; Ducret, Thomas; Vacher, Anne-Marie; Barrow, Paul A.; Flynn, Robin J.; Vacher, Pierre; Legembre, Patrick
Authors
Doriane Sans�au
Matthieu Le Gallo
Marine Malleter
Nicolas Levoin
Roselyne Viel
Lucie Morere
Aubin Penna
Patrick Blanco
Alain Dupuy
Florence Poizeau
Alain Fautrel
Julien Seneschal
Florence Jouan
Jerome Ritz
Edouard Forcade
Nathalie Rioux
C�cile Contin-Bordes
Thomas Ducret
Anne-Marie Vacher
Paul A. Barrow
Robin J. Flynn
Pierre Vacher
Patrick Legembre
Abstract
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.
Citation
Poissonnier, A., Sanséau, D., Le Gallo, M., Malleter, M., Levoin, N., Viel, R., …Legembre, P. (2016). CD95-Mediated Calcium Signaling Promotes T Helper 17 Trafficking to Inflamed Organs in Lupus-Prone Mice. Immunity, 45(1), 209-223. https://doi.org/10.1016/j.immuni.2016.06.028
Journal Article Type | Article |
---|---|
Acceptance Date | May 10, 2016 |
Publication Date | Jul 19, 2016 |
Deposit Date | Aug 23, 2017 |
Publicly Available Date | Aug 23, 2017 |
Journal | Immunity |
Print ISSN | 1074-7613 |
Electronic ISSN | 1097-4180 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 45 |
Issue | 1 |
Pages | 209-223 |
DOI | https://doi.org/10.1016/j.immuni.2016.06.028 |
Public URL | https://nottingham-repository.worktribe.com/output/800413 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S1074761316302503 |
Contract Date | Aug 23, 2017 |
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