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 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)

Full text not available from this repository.


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.

Item Type: Article
Keywords: Calcium; CD95; Inflammation; Lupus; Sphingosine-1 phosphate; Th17 cell
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Depositing User: Eprints, Support
Date Deposited: 18 Jul 2016 08:06
Last Modified: 04 May 2020 17:52

Actions (Archive Staff Only)

Edit View Edit View