Abstract TMP28: De Novo Fatty Acid Synthesis In Cd4 + T Cells After Cerebral Ischemic Stroke - A New Target of Post-stroke Immune Modulation

• Published in: Stroke (1970) 2019-02, Vol.50 (Suppl_1)
• Main Authors: Wang, Xin, Zhou, Yuxi, Zhu, Ziyu, Li, Yan, Li, Peiying, Yu, Weifeng
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.50.suppl_1.TMP28

Abstract only Stroke elicits activation and differentiation of CD4 + T cells into Th17 and Tregs, in which de novo fatty acid synthesis plays an important role. Caloric restriction is neuroprotective against cerebral ischemic brain injury, but its impact on post-stroke immune cell metabolism are yet to be explored. We hypothesize that 1) increased de novo fatty acid synthesis in peripheral CD4 + T cells after ischemic stroke could be suppressed by caloric restriction pretreatment, resulting in improved Th17/Treg balance in the peripheral and reduced neuroinflammation; 2) Acetyl-CoA Carboxylase 1 (ACC1), the rate limiting enzyme of de novo fatty acid synthesis, might be an important target of pre-stroke caloric restriction. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAO) for 60 minutes in mice. Caloric restriction were performed for 4 weeks before MCAO with 30% reduction of feeds. Each group contains 5 or 6 mice. Mechanistically, ACC1 was either pharmacologically inhibited by Soraphen A at 2 hours after MCAO or genetically depleted by conditional knockout of ACC1 in CD4 + T cells. The mRNA levels of inflammatory factors were measured by reverse-transcriptase polymerase chain reaction, T cells in the ischemic brain and periphery were evaluated using flow cytometry and immunohistochemistry. Both real-time PCR and flow cytometry confirmed an increased expression of ACC1 in CD4 + T cells but not in B cells and macrophage after stroke, while inhibiting ACC1 by Soraphen A reduced ischemic brain injury and attenuated neuroinflammation after stroke. Pre-stroke caloric restriction significantly inhibited ACC1 expression in CD4 + T cells and altered the differentiation of CD4 + T cells to Th17 or Treg cells and after stroke. Using CD4 cre ACC1 fl/fl mice, we showed that ACC1 deficiency in CD4 + T cells attenuated caloric restriction afforded neuroprotection and preservation of peripheral Th17/Treg balance after stroke. In conclusion, c erebral ischemic stroke elicits de novo fatty acid synthesis in peripheral CD4 + T cells and down-regulation of ACC1 might underlie the peripheral mechanism of caloric restriction in combatting neuroinflammation after cerebral ischemic stroke.