Agonistic anti‐CD27 antibody ameliorates EAE by suppressing IL‐17 production

作者：Isabel Vogel, Valérie Acolty, Tibor Keler, Stanislas Goriely, Oberdan Léo, Muriel Moser · 发表于：European Journal of Immunology · 年份：2022 · DOI：10.1002/eji.202149698 · 被引用次数：7 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

ABSTRACT 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 CD27 flox/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.