2. Academic Validation
  3. Negative effects of brain regulatory T cells depletion on epilepsy

Negative effects of brain regulatory T cells depletion on epilepsy

  • Prog Neurobiol. 2022 Oct;217:102335. doi: 10.1016/j.pneurobio.2022.102335.
Jiong Yue 1,  Ruxiang Xu 2,  Cheng Yin 2,  Hui Yang 3,  Chunqing Zhang 3,  Dongdong Zhao 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: yuejiong01@163.com.
  • 2 Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
  • 3 Comprehensive Epilepsy Center, Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 4 Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: Zhaoddsrm@protonmail.com.
PMID: 35931355 DOI: 10.1016/j.pneurobio.2022.102335
Abstract

The infiltration of immune cells is observed in the epileptogenic zone; however, the relationship between epilepsy and regulatory T cells (Tregs) remains only partially understood. We aimed to investigate brain-infiltrating Tregs to reveal their underlying role in epilepsy. We analyzed the infiltration of Tregs in the epileptogenic zones from patients with epilepsy and a pilocarpine-induced temporal lobe epilepsy (TLE) model. Next, we evaluated the effects of brain Treg depletion on neuroinflammation, neuronal loss, oxidative stress, seizure activity and behavioral changes in the pilocarpine model. We also explored the impact of Treg expansion in the brain on seizure activity. There were a large number of Tregs in the epileptogenic zones of human and experimental epilepsy. The number of brain Tregs was negatively correlated with the frequency of seizures in patients with epilepsy. Our further findings demonstrated that brain Treg depletion promoted astrocytosis, microgliosis, inflammatory cytokine production, oxidative stress, and neuronal loss in the hippocampus after status epilepticus (SE). Moreover, brain Treg depletion increased seizure activity and contributed to behavioral impairments in experimental chronic TLE. Interestingly, intracerebroventricular injection of CCL20 amplified Tregs in brain tissue, thereby inhibiting seizure activity. Taken together, our study highlights the therapeutic potential of regulating Tregs in epileptic brain tissue.

Keywords

Neuroinflammation; Neuronal loss; Oxidative stress; Regulatory T cells; Seizure activity; Temporal lobe epilepsy.

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