Post-Stroke Microglia Induce Sirtuin2 Expression to Suppress the Anti-inflammatory Function of Infiltrating Regulatory T Cells

Shu, Long; Xu, Chao-Qing; Yan, Zhaoyi; Yan, Yang; Jiang, Shi-Zhu; Yingrui, Wang

doi:10.1007/s10753-019-01057-3

Cited by 35 publications

(38 citation statements)

References 40 publications

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“…Nevertheless, lymphocytes in the circulation swiftly decreased 3 h after MCAO. In accordance with this finding, previous reports have shown that migration of immune cells is a process which almost coincides with MCAO [ 53 , 54 , 55 ]. However, the S1P gradient alone cannot solely account for immune cell migration to the brain as also sham S1P levels in the brain superseded sham S1P levels in the circulation.…”

Section: Discussionsupporting

confidence: 90%

“…Reports are accumulating that this process applies to adaptive lymphocytes, too. In that respect, various T H cell populations and T REG cells in the ischemic hemisphere have been found to amass on the first day after MCAO [ 53 , 54 , 55 ]. Moreover, it can be argued that neurons are an important source of S1P [ 56 ], suggesting that as cerebral blood flow (CBF) decreases and neuronal damage worsens, the release of S1P into the ischemic core could contribute to the maintained high S1P levels [ 40 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

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A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke

Lucaciu

Kühn

Trautmann

et al. 2020

IJMS

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Emerging evidence suggests a complex relationship between sphingosine 1-phosphate (S1P) signaling and stroke. Here, we show the kinetics of S1P in the acute phase of ischemic stroke and highlight accompanying changes in immune cells and S1P receptors (S1PR). Using a C57BL/6 mouse model of middle cerebral artery occlusion (MCAO), we assessed S1P concentrations in the brain, plasma, and spleen. We found a steep S1P gradient from the spleen towards the brain. Results obtained by qPCR suggested that cells expressing the S1PR type 1 (S1P1+) were the predominant population deserting the spleen. Here, we report the cerebral recruitment of T helper (TH) and regulatory T (TREG) cells to the ipsilateral hemisphere, which was associated with differential regulation of cerebral S1PR expression patterns in the brain after MCAO. This study provides insight that the S1P-S1PR axis facilitates splenic T cell egress and is linked to the cerebral recruitment of S1PR+ TH and TREG cells. Further insights by which means the S1P-S1PR-axis orchestrates neuronal positioning may offer new therapeutic perspectives after ischemic stroke.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke

Lucaciu

Kühn

Trautmann

et al. 2020

IJMS

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“…Previous reports have shown T cells play a key role in secondary neuroinflammation following stroke [9][10][11] . T cells and lymphocytes have also been identified as the main substances in the regulation of inflammatory response after brain injury, especially T cells play a major role, and regulatory T cells (Tregs) can inhibit neuroinflammatory damage [11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats

Zhang

Zhai

Qian

et al. 2020

Biological & Pharmaceutical Bulletin

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Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S rDNA sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume was also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.

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“…Similarly, a study demonstrated that poststroke microglia suppress the anti‐inflammatory function of infiltrating Tregs. A novel mechanism of microglial immunoregulatory activity through the Sirtuin2/HIF‐1α pathway was identified . Recently, a study reported that the CD3+CD4‐CD8‐T‐cell (double‐negative T cell; DNT) population is significantly upregulated in the peripheral blood of acute stroke patients.…”

Section: Microglia‐neighboring Cells Crosstalk and Interventions For mentioning

confidence: 99%

“…A novel mechanism of microglial immunoregulatory activity through the Sirtuin2/HIF-1α pathway was identified. 110 Recently, a study reported that the CD3+CD4-CD8-T-cell (double-negative T cell; DNT) population is significantly upregulated in the peripheral blood of acute stroke patients. It is intriguing that infiltrating DNTs are located close to the microglial population in the ischemic brain territories of both MCAO mice and stroke patients.…”

Section: T Cells or By Releasing Inflammatory Cytokines Via Tregs Andmentioning

confidence: 99%

Potential microglia‐based interventions for stroke

Huang

Yang

et al. 2020

CNS Neurosci Ther

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A large number of families worldwide suffer from the physical and mental burden posed by stroke. An increasing number of studies aimed at the prevention and treatment of stroke have been conducted. Specifically, manipulating the immune response to stroke is under intense investigation. Microglia are the principal immune cells in the brain and are the first line of defense against the pathophysiology induced by stroke. Increasing evidence has suggested that microglia play diverse roles that depend on dynamic interactions with neurons, astrocytes, and other neighboring cells both in the normal brain and under pathological conditions, including stroke. Moreover, there are dynamic alterations in microglial functions with respect to aging and sex differences in the human brain, which offer a deep understanding of the conditions of stroke patients of different ages and sex. Hence, we review the dynamic microglial reactions caused by aging, sex, and crosstalk with neighboring cells both in normal conditions and after stroke and relevant potential interventions.

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Post-Stroke Microglia Induce Sirtuin2 Expression to Suppress the Anti-inflammatory Function of Infiltrating Regulatory T Cells

Cited by 35 publications

References 40 publications

A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke

A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke

Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats

Potential microglia‐based interventions for stroke

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