| Autor: |
Sandrine Juillard, Annie Karakeussian-Rimbaud, Marie-Hélène Normand, Julie Turgeon, Charlotte Veilleux-Trinh, Alexa C. Robitaille, Joyce Rauch, Andrzej Chruscinski, Nathalie Grandvaux, Éric Boilard, Marie-Josée Hébert, Mélanie Dieudé |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Journal of Translational Autoimmunity, Vol 9, Iss , Pp 100250- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-9090 |
| DOI: |
10.1016/j.jtauto.2024.100250 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
