Vogel I, Acolty V, Keler T, Goriely S, Leo O, Moser M.Eur J Immunol. 2022. doi: 10.1002/eji.202149698.
CD27/CD70 costimulation enhances T-cell survival, memory formation and Th1-cell differentiation and effector function. In addition to promoting Th1 responses, CD27 signalling has been shown to exert a negative regulatory role on IL-17 production, resulting in increased sensitivity of CD27 KO mice to experimental autoimmune encephalomyelitis (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 central nervous system (CNS) while IFNγ 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.
Why present this story?
Well it talks about CD27 as a potential target for MS, and it is music to my ears…but perhaps for all the wrong reasons. CD27 is found on a number of T cells and this is the study matter for the paper. They take a non killing CD27 specific antibody and it inhibits EAE…I say yep blocK CD4 T cellls and it inhibits EAE because it is T cell mediated. However CD27 is one of the few markers of memory B cells. So if you chase CD27 T cells, you should affect memory B cells. If you had a depleting antibody if may get rid of memory B cells and some T cells, I would predict this will would work but the antibody in clinical use is not depleting. This called varlilumab. So will this mousey data encourage people to do studies in humans?
I dont’ know
There is no point in doing this study to get an answer in EAE (a) CD27 is not a marker of memory B cells in mice and (b) CD19 depletion in rodents has no to a marginal effect….because EAE is T cell mediated.
Maybe sone company may do it, when we tried to get some funding people, the idea wasn’t liked
CoI None relevant
Disclaimer these are the authors view