Fiche du document
16 septembre 2024
- handle: 10670/1.xt0rsc
- doi: 10.1016/j.jtauto.2024.100250
Ce document est mis à disposition selon les termes de la Licence Creative Commons Attribution - Pas d’utilisation commerciale 4.0 International. / This work is licensed under a Creative Commons Attribution - NonCommercial 4.0 International License. , https://creativecommons.org/licenses/by-nc/4.0/deed.fr
Mots-clés
ApoExos Autoantibodies Anti-LG3 Systemic lupus erythematosus (SLE) Toll-like receptors (TLR)Sujets proches
B lymphocytes Bursa equivalent cells Bone marrow derived cellsCiter ce document
Sandrine Juillard et al., « Vascular injury derived apoptotic exosome-like vesicles trigger autoimmunity », Papyrus : le dépôt institutionnel de l'Université de Montréal, ID : 10.1016/j.jtauto.2024.100250
Métriques
Partage / Export
Résumé
According to a central tenet of classical immune theory, a healthy immune system must avoid self-reactive lymphocyte clones but we now know that B cells repertoire exhibit some level of autoreactivity. These autoreactive B cells are thought to rely on self-ligands for their clonal selection and survival. Here, we confirm that healthy mice exhibit self-reactive B cell clones that can be stimulated in vitro by agonists of toll-like receptor (TLR) 1/2, TLR4, TLR7 and TLR9 to secrete anti-LG3/perlecan. LG3/perlecan is an antigen packaged in exosome-like structures released by apoptotic endothelial cells (ApoExos) upon vascular injury. We demonstrate that the injection of ApoExos in healthy animals activates the IL-23/IL-17 pro-inflammatory and autoimmune axis, and produces several autoantibodies, including anti-LG3 autoantibodies and hallmark autoantibodies found in systemic lupus erythematosus. We also identify γδT cells as key mediators of the maturation of ApoExos-induced autoantibodies in healthy mice. Altogether we show that ApoExos released by apoptotic endothelial cells display immune-mediating functions that can stimulate the B cells in the normal repertoire to produce autoantibodies. Our work also identifies TLR activation and γδT cells as important modulators of the humoral autoimmune response induced by ApoExos.