CD8 T cell-derived perforin aggravates secondary spinal cord injury through destroying the blood-spinal cord barrier

Liu, Zhaoxiang; Zhang, Hua; Xia, H. Amy; Wang, Baocheng; Zhang, Renwen; Zeng, Qun; Guo, Lang; Shen, Kui; Wang, BaTa; Zhong, Yanheng; Li, Zhizhong; Sun, Guodong

doi:10.1016/j.bbrc.2019.03.002

Cited by 35 publications

(24 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased GrB expression (which correlated with infiltrated CD8 + T cells) has also been observed in a rat model of SCI (Chaitanya et al, 2009) and ischemic stroke (Chaitanya et al, 2010). Our findings are supported by a recent SCI study, which found that perforin (mainly produced by CD8 + T cells) causes inflammation and blood-spinal cord barrier damage, as perforin À/À mice had improved outcomes, in the acute/subacute phase (Liu et al, 2019). This is important since it confirms that functionally active CD8 + T cells that secrete perforin/GrB, as observed in our TBI study, can promote secondary damage in the CNS.…”

Section: Discussionsupporting

confidence: 87%

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

et al. 2019

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 87%

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…To evaluate functional recovery after SCI, motor-evoked potentials (MEPs) of mice 4 weeks post-injury were analyzed using electromyography according to previous studies [59][60][61]. Mice were firstly anesthetized with 10% chloral hydrate solution.…”

Section: Electrophysiologymentioning

confidence: 99%

Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization

Liu

Rong

Wang

et al. 2020

J Neuroinflammation

373

274

View full text Add to dashboard Cite

Background: Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction with high disability and mortality. In recent years, mesenchymal stem cell (MSC)-secreted nano-sized exosomes have shown great potential for promoting functional behavioral recovery following SCI. However, MSCs are usually exposed to normoxia in vitro, which differs greatly from the hypoxic micro-environment in vivo. Thus, the main purpose of this study was to determine whether exosomes derived from MSCs under hypoxia (HExos) exhibit greater effects on functional behavioral recovery than those under normoxia (Exos) following SCI in mice and to seek the underlying mechanism. Methods: Electron microscope, nanoparticle tracking analysis (NTA), and western blot were applied to characterize differences between Exos and HExos group. A SCI model in vivo and a series of in vitro experiments were performed to compare the therapeutic effects between the two groups. Next, a miRNA microarray analysis was performed and a series of rescue experiments were conducted to verify the role of hypoxic exosomal miRNA in SCI. Western blot, luciferase activity, and RNA-ChIP were used to investigate the underlying mechanisms. Results: Our results indicate that HExos promote functional behavioral recovery by shifting microglial polarization from M1 to M2 phenotype in vivo and in vitro. A miRNA array showed miR-216a-5p to be the most enriched in HExos and potentially involved in HExos-mediated microglial polarization. TLR4 was identified as the target downstream gene of miR-216a-5p and the miR-216a-5p/TLR4 axis was confirmed by a series of gain-and loss-offunction experiments. Finally, we found that TLR4/NF-κB/PI3K/AKT signaling cascades may be involved in the modulation of microglial polarization by hypoxic exosomal miR-216a-5p. Conclusion: Hypoxia preconditioning represents a promising and effective approach to optimize the therapeutic actions of MSC-derived exosomes and a combination of MSC-derived exosomes and miRNAs may present a minimally invasive method for treating SCI.

show abstract

“…After SCI, CD8 + T cells can produce perforin. Perforin destroys tight‐junction proteins in the blood‐spinal cord barrier, allows infiltration of inflammatory cytokines and aggravates the injury 2 …”

Section: Cd8+ T Cells In the Cns Post‐traumatic Injurymentioning

confidence: 99%

“…Pharmacological exhaustion of CD8 + T cells can improve neurological outcomes and produce a neuroprotective Th2/Th17 immunological transition 28 . Third, CD8 + T cells can aggravate the injury by producing perforin 2 …”

Section: Cd8+ T Cells In the Cns Post‐traumatic Injurymentioning

confidence: 99%

“…Central nervous system (CNS) post‐traumatic injury usually results in irreversible impairment. It causes necrosis and apoptosis of neurons and glia due to the initial injury, followed by an expansion of secondary degeneration caused by the apoptosis of initially undamaged neurons 1,2 . There are two forms by which traumatic CNS injury may occur; specifically, traumatic brain injury (TBI) or spinal cord injury (SCI).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

T‐cell infiltration, contribution and regulation in the central nervous system post‐traumatic injury

Wang

et al. 2021

Cell Proliferation

View full text Add to dashboard Cite

T cells participate in the repair process and immune response in the CNS post‐traumatic injury and play both a beneficial and harmful role. Together with nerve cells and other immune cells, they form a microenvironment in the CNS post‐traumatic injury. The repair of traumatic CNS injury is a long‐term process. T cells contribute to the repair of the injury site to influence the recovery. Recently, with the advance of new techniques, such as mass spectrometry‐based flow cytometry, modern live‐cell imaging, etc, research focusing on T cells is becoming one of the valuable directions for the future therapy of traumatic CNS injury. In this review, we summarized the infiltration, contribution and regulation of T cells in post‐traumatic injury, discussed the clinical significance and predicted the future research direction.

show abstract

CD8 T cell-derived perforin aggravates secondary spinal cord injury through destroying the blood-spinal cord barrier

Cited by 35 publications

References 34 publications

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization

T‐cell infiltration, contribution and regulation in the central nervous system post‐traumatic injury

Contact Info

Product

Resources

About