T-cell receptor signaling modulated by the co-receptors: Potential targets for stroke treatment

Liu, Yuanyuan; Chen, Shuai; Liu, Simon; Wallace, Kevin L.; Zille, Marietta; Zhang, Jiewen; Wang, Jian; Jiang, Chao

doi:10.1016/j.phrs.2023.106797

Cited by 13 publications

(14 citation statements)

References 203 publications

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“…[26][27][28] The activation of T cells is triggered by specific surface receptors that identify antigens and initiate autoimmune responses. 29,30 Compared to innate immune responses, autoreactive T cells can cause direct harm to neurons and glial cells and indirectly affect neuronal function and survival through the release of pro-inflammatory cytokines (IFNγ, IL-1β, TNFα, IL-12) and chemokines (CCL2 and CCL5, among others). 31 CD4 + T cells are categorized into effector (Teff) and regulatory (Treg) T cells, which work together to maintain immune balance.…”

Section: Cellular Immune Responsementioning

confidence: 99%

Role of dendritic cells in spinal cord injury

Han,

Zhang,

Yan

et al. 2024

CNS Neurosci Ther

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BackgroundInflammation can worsen spinal cord injury (SCI), with dendritic cells (DCs) playing a crucial role in the inflammatory response. They mediate T lymphocyte differentiation, activate microglia, and release cytokines like NT‐3. Moreover, DCs can promote neural stem cell survival and guide them toward neuron differentiation, positively impacting SCI outcomes.ObjectiveThis review aims to summarize the role of DCs in SCI‐related inflammation and identify potential therapeutic targets for treating SCI.MethodsLiterature in PubMed and Web of Science was reviewed using critical terms related to DCs and SCI.ResultsThe study indicates that DCs can activate microglia and astrocytes, promote T‐cell differentiation, increase neurotrophin release at the injury site, and subsequently reduce secondary brain injury and enhance functional recovery in the spinal cord.ConclusionsThis review highlights the repair mechanisms of DCs and their potential therapeutic potential for SCI.

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Section: Cellular Immune Responsementioning

confidence: 99%

Role of dendritic cells in spinal cord injury

Han,

Zhang,

Yan

et al. 2024

CNS Neurosci Ther

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“…Although the specific details of this pathway in the context of CNS injury are not fully understood, it is essential to note that the pro‐inflammatory response of particular cytokines, known as Th1 and Th17 cytokines, can worsen nerve damage caused by inflammation. 21 , 107 This finding leads us to believe that a pathway involving various components such as IL‐15, IL‐12, CD8 + T cell, CD4 + T cell, NK cell, XCL1, XCR1 + dendritic cell, IFN‐γ, Th0 cells, Th1 cells, and Th17 cell may have a pro‐inflammatory effect after TBI and SCI. Blocking any part of this pathway could have positive effects and ultimately improve the prognosis of neurological injuries, making it a promising therapeutic approach (Figures 1 and 2 ).…”

Section: The Role Of Upstream and Downstream Pathways Of The Xcl1‐xcr...mentioning

confidence: 99%

Inflammatory response in traumatic brain and spinal cord injury: The role of XCL1‐XCR1 axis and T cells

Zhang,

Han,

Yan

et al. 2024

CNS Neurosci Ther

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BackgroundTraumatic brain injury (TBI) and spinal cord injury (SCI) are acquired injuries to the central nervous system (CNS) caused by external forces that cause temporary or permanent sensory and motor impairments and the potential for long‐term disability or even death. These conditions currently lack effective treatments and impose substantial physical, social, and economic burdens on millions of people and families worldwide. TBI and SCI involve intricate pathological mechanisms, and the inflammatory response contributes significantly to secondary injury in TBI and SCI. It plays a crucial role in prolonging the post‐CNS trauma period and becomes a focal point for a potential therapeutic intervention. Previous research on the inflammatory response has traditionally concentrated on glial cells, such as astrocytes and microglia. However, increasing evidence highlights the crucial involvement of lymphocytes in the inflammatory response to CNS injury, particularly CD8+ T cells and NK cells, along with their downstream XCL1‐XCR1 axis.ObjectiveThis review aims to provide an overview of the role of the XCL1‐XCR1 axis and the T‐cell response in inflammation caused by TBI and SCI and identify potential targets for therapy.MethodsWe conducted a comprehensive search of PubMed and Web of Science using relevant keywords related to the XCL1‐XCR1 axis, T‐cell response, TBI, and SCI.ResultsThis study examines the upstream and downstream pathways involved in inflammation caused by TBI and SCI, including interleukin‐15 (IL‐15), interleukin‐12 (IL‐12), CD8+ T cells, CD4+ T cells, NK cells, XCL1, XCR1+ dendritic cells, interferon‐gamma (IFN‐γ), helper T0 cells (Th0 cells), helper T1 cells (Th1 cells), and helper T17 cells (Th17 cells). We describe their proinflammatory effect in TBI and SCI.ConclusionsThe findings suggest that the XCL1‐XCR1 axis and the T‐cell response have great potential for preclinical investigations and treatments for TBI and SCI.

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“…This includes the recruitment of peripheral immune cells to the damaged brain. After an innate immune response initiated by microglia or macrophages, adaptive immune responses associated with T lymphocytes contribute to the complex pathophysiology of stroke 15 . Invasive T cells interact closely with active astrocytes and have a progressive proin ammatory phenotype after ischemic stroke, as evidenced by increased expression of the T cell activation markers CD44 and CD25 and the corresponding transcription factors T-bet and RORC.…”

Section: Introductionmentioning

confidence: 99%

Causal role of immune cells in ischemic stroke: a Mendelian Randomization study

Dong,

Li,

Xiang

et al. 2024

Preprint

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Background Conventional observational designs face challenges in studying this relationship, as confounding factors, reverse causality, minor exposure factors and multiple tests cannot be completely eliminated. There is currently a lack of MR studies concerning immune cells and the risk of ischemic stroke. This particular study offers a novel perspective on risk prediction for ischemic stroke. Objective To investigate the causal relationship between immune cells and ischemic stroke through Mendelian randomization analysis. Methods A complete two-sample Mendelian randomization (MR) analysis was utilized to ascertain the causative relationship between immune cells and ischemic stroke. Using publicly available genetic data, we investigated the causal association between 731 immune cells and the risk of ischemic stroke. Four immune characteristics were included: relative cells (RC), absolute cells (AC), median fluorescence intensity (MFI), and morphological parameters (MP). MR-Egger, Weighted median, Inverse variance weighted (IVW), Weighted mode, Simple mode, and MRPRESS were utilized for analysis. Heterogeneity and horizontal pleiotropy tests were also conducted. Results Mendelian randomization analysis showed that 32 of the 731 immune cells had a robust causal relationship with ischemic stroke, among which 15 immune cells such as IgD−CD27− %B cell (β = 0.033, 95%CI = 1.002 ~ 1.065, p = 0.037), IgD+ CD24 + AC (β = 0.045, 1.010 ~ 1.082, p = 0.012), CD25hi CD45RA−CD4 not Treg %T cell (β = 0.022, 95%CI = 1.002 ~ 1.042, p = 0.028) and soon. CD62L−HLADR++ monocyte AC (β =-0.053, 95% CI = 0.914 ~ 0.985, p = 0.005), CD33br HLA DR+ CD14− AC (β =-0.017, 95% CI = 0.972 ~ 0.995, p = 0.004), EM DN (CD4−CD8−) %DN (β =-0.014, 95% CI = 0.975 ~ 0.997, p = 0.014), etc. There exists a strong inverse causal link for ischemic stroke. Conclusion Our study has demonstrated a close genetic link between immune cells and ischemic stroke. Fifteen immune cells such as IgD−CD27− %B cell, IgD+ CD24+ AC, CD25hi CD45RA−CD4 not Treg %T cell have robust positive causal associations with ischemic stroke, and seventeen immune cells such asCD62L− HLA DR++ monocyte AC, CD33br HLA DR+ CD14− AC, EM DN (CD4−CD8−) %DN have robust positive causal associations with ischemic stroke. A strong inverse causal relationship with ischemic stroke offers direction for forthcoming clinical studies.

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T-cell receptor signaling modulated by the co-receptors: Potential targets for stroke treatment

Cited by 13 publications

References 203 publications

Role of dendritic cells in spinal cord injury

Role of dendritic cells in spinal cord injury

Inflammatory response in traumatic brain and spinal cord injury: The role of XCL1‐XCR1 axis and T cells

Causal role of immune cells in ischemic stroke: a Mendelian Randomization study

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