Apolipoprotein E and its mimetic peptide suppress Th1 and Th17 responses in experimental autoimmune encephalomyelitis

• The effect of apoE on Th17 response was systematically studied.
• ApoE exerts this suppressive function not through lipid transport.
• ApoE ameliorates disease progression and the pathological damage in the CNS.
• ApoE suppresses Th1 and Th17 responses in the peripheral and the CNS.
• The mechanism is associated with the modulation of cytokines release in macrophages.

Apolipoprotein E (apoE) has been detected to possess anti-inflammatory properties that can contribute to protection against experimental autoimmune encephalomyelitis (EAE). However, its impact on Th1 and Th17 responses in EAE is unclear. In this study, we induced EAE in apoE−/− mice and wild-type mice. We observed that the absence of apoE resulted in the increased proportion of Th1 and Th17 cells in the spleens and brains, as well as up-regulated expressions of proinflammatory cytokines (IL-17, IFN-γ, TNF-α, IL-12, IL-1β and IL-6) and transcription factors (RORγt and T-bet) in the CNS. ApoE−/− mice also showed the increased release of proinflammatory cytokines by macrophages in vitro. In addition, we used a mimetic peptide of apoE, which mimic the functions of apoE except for lipid transport. ApoE mimetic peptide could reverse the above negative effect in EAE. Thus, apoE can modulate Th1 and Th17 responses, likely through its inhibitory effect on the secretion of cytokines by macrophages. Our result also suggests that apoE mimetic peptide might be developed into a therapeutic agent for multiple sclerosis.