Fiche publication
Date publication
juillet 2018
Journal
JCI insight
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUMORTIER Hélène
,
Pr GOTTENBERG Jacques-Eric
Tous les auteurs :
Sawaf M, Fauny JD, Felten R, Sagez F, Gottenberg JE, Dumortier H, Monneaux F
Lien Pubmed
Résumé
Coinhibitory receptors play an important role in the prevention of autoimmune diseases, such as systemic lupus erythematosus (SLE), by limiting T cell activation. B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. The role of BTLA in the pathogenesis of autoimmune diseases in humans and, more specifically, in SLE is largely unknown. We investigated BTLA expression on various T cell subsets, and we did not observe significant variations of BTLA expression between lupus patients and healthy controls. However, the enhancement of BTLA expression after activation was significantly lower in SLE patients compared with that in healthy controls. Furthermore, we found an impaired capacity of BTLA to inhibit T cell activation in SLE due to a poor BTLA recruitment to the immunological synapse following T cell stimulation. Finally, we demonstrated that defective BTLA function can be corrected by restoring intracellular trafficking and by normalizing the lipid metabolism in lupus CD4+ T cells. Collectively, our results evidence that the BTLA signaling pathway is altered in SLE T cells and highlight the potential of targeting this pathway for the development of new therapeutic strategies in lupus.
Mots clés
Autoimmunity, Immunology, Lupus
Référence
JCI Insight. 2018 Jul 12;3(13):
