par Vogel, Isabel ;Acolty, Valérie ;Keler, Tibor;Goriely, Stanislas ;Leo, Oberdan ;Moser, Muriel
Référence European Journal of Immunology, 52, 10, page (1620-1629)
Publication Publié, 2022-10-01
Référence European Journal of Immunology, 52, 10, page (1620-1629)
Publication Publié, 2022-10-01
Article révisé par les pairs
Résumé : | CD27/CD70 costimulation enhances T-cell survival, memory formation and Th1-cell differentiation and effector function. In addition to promoting Th1 responses, CD27 signaling has been shown to exert a negative regulatory role on IL-17 production, resulting in increased sensitivity of CD27 KO mice to EAE. By inducing EAE in full CD27 KO mice, and in a novel, T-cell specific CD27 KO mouse strain (CD4-Cre x CD27flox/flox ), we demonstrate herein that CD27 engagement by its natural ligand (CD70) suppresses IL-17 production in a cell autonomous fashion. We further show that CD27 engagement by an agonistic antibody given after EAE induction or at symptom onset similarly suppresses IL-17 production by activated CD4+ T cells infiltrating the inflamed CNS while IFN-γ production was unaffected, leading to an amelioration of inflammatory-related symptoms. These findings propose CD27 costimulation as a potential candidate for therapeutic manipulation to treat autoimmune and autoinflammatory diseases characterized by excessive IL-17 production. |