CD8 T cell–Derived Perforin and TNF-α Are Crucial Mediators of Neuronal Destruction in Experimental Autoimmune Enteric Ganglionitis

Sánchez‐Ruiz, Monica; Iorgu, Ana-Maria; Küster, Florian; Hellmich, Martin; Brunn, Anna; Deckert, Martina

doi:10.1016/j.ajpath.2021.02.021

Cited by 7 publications

(3 citation statements)

References 45 publications

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“…In autoimmune enteric ganglionitis, the effect of CD8 T cells on neuronal destruction is perforin dependent [ 27 ]. Inflammatory stress has been confirmed as a major reason for myelin and neuronal injury.…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam Attenuates the Spinal Cord Injury Induced by Acute Trauma via Suppressing the Expression of Perforin

Xia

Huang

Liu

et al. 2022

Computational and Mathematical Methods in Medicine

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The spinal cord injury (SCI) is one of the major reasons causing the motor dysfunctions of the patients. At present, few therapeutic strategies can effectively improve the symptom of SCI. Levetiracetam has been confirmed to alleviate the injury of nerve cells, while its functions in SCI remains unclear. In this study, C57BL/6J mice were used to establish SCI models to observe the effect of levetiracetam on SCI. The mice were fed with 180 mg/kg levetiracetam when suffering from SCI, and Basso mouse score (BMS) and CatWalk-assisted gait analysis were used to observe the motor functions of the mice. Nissl staining and TUNEL staining were used to observe the injury of nerve cells. The abundance of inflammatory factors was measured by ELISA. The permeability of blood-spinal cord barrier (BSCB) in mice was detected with macrophage infiltration analysis. Moreover, the abundance of perforin in the tissues was detected by western blot. The results showed that the SCI mice treated with levetiracetam exhibited lighter motor dysfunction compared with the mice treated with saline. Levetiracetam can effectively reduce the inflammatory reactions and alleviate apoptosis of the nerve cells. Moreover, levetiracetam remarkably decreased the BSCB permeability of SCI mice. Besides, it was also found that levetiracetam can significantly inhibit the expression of perforin. In conclusion, this study suggests that levetiracetam can attenuate the injury of BSCB to block the progression of SCI via suppressing the expression of perforin.

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Section: Discussionmentioning

confidence: 99%

Levetiracetam Attenuates the Spinal Cord Injury Induced by Acute Trauma via Suppressing the Expression of Perforin

Xia

Huang

Liu

et al. 2022

Computational and Mathematical Methods in Medicine

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“… 51 TNF-α is also a key effector molecule for CD8+ T cells and NK cells. 52 T helper 1 lymphocyte and cytotoxic CD8+ T cell responses are considered key factors that are necessary to achieve antitumor effects. 53 The antitumor activity of TLR agonists was first reported as early as the 18th century when bacterial infections had the potential to inhibit cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Wu,

Chen,

Huang

et al. 2023

IJGM

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Introduction The relationship between the expression of opioid-associated receptors and cancer outcomes is complex and varies among studies. Methods This study focused on six opioid-related receptors (OPRM1, OPRD1, OPRK1, OPRL1, OGFR, and TLR4) and their impact on cancer patient survival. Bioinformatics analysis was conducted on 33 cancer types from The Cancer Genome Atlas database to examine their expression, clinical correlations, mechanisms in the tumor microenvironment, and potential for immunotherapy. Due to significantly lower expression of OPRM1, OPRD1, and OPRK1 compared to OGFR and TLR4, the analysis concentrated on the latter two genes. Results OGFR was highly expressed in 16 tumor types, while TLR4 showed low expression in 13. Validation from external samples, the Gene Expression Omnibus, and the Human Protein Atlas supported these findings. The diagnostic value of these two genes was demonstrated using the Genotype-Tissue Expression database. Univariate Cox regression models and Kaplan-Meier curves confirmed OGFR’s impact on prognosis in a cancer type-specific manner, while high TLR4 expression was associated with a favorable prognosis. Analysis of the tumor microenvironment using a deconvolution algorithm linked OGFR to CD8+ T cells and TLR4 to macrophages. Single-cell datasets further validated this correlation. In 25 immune checkpoint blockade treatment cohorts, TLR4 expression showed promise as an immunotherapy efficacy predictor in non-small cell lung cancer, urothelial carcinoma, and melanoma. Conclusion In a pan-cancer analysis of 33 tissues, OGFR was consistently highly expressed, while TLR4 had low expression. Both genes have diagnostic and prognostic significance and are linked to immune cells in the tumor microenvironment. TLR4 has potential as an immunotherapeutic response marker.

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“…CD8 + T cells are one of the important anti-tumor cells. They kill tumor cells specifically through perforin granzyme, Fas-FasL and TNF-TNFR ( 16 ). γδ T cells are a kind of non-MHC restricted innate T lymphocytes that are widely distributed in peripheral blood and mucosal tissues.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and significance of T lymphocyte subsets in peripheral blood of osteosarcoma mice

Liu¹,

Xu²,

Xu³

et al. 2022

Transl Cancer Res TCR

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Background Osteosarcoma (OS) is the most common malignant bone tumor, which often has lung metastasis. The survival rate after tumor metastasis is very low. Treatments including the antitumor immunocompetence of innate immune cells are found favorable for OS tumor. However, as a major means of early tumor detection, there are still few studies on T cells in peripheral blood of OS patients. Methods OS cells were implanted into the femoral bone marrow cavity of C3H/HeN mice to construct OS model. The proportion of T lymphocyte subsets in peripheral blood of mice was detected by flow cytometry on the 14 th and 21 st days after modeling. Results Compared with sham operation group, on the 14 th day after operation, the proportion of γδT cells and CD4 + regulatory T cells (Tregs) showed significantly higher level while other subsets didn’t have obvious difference. On the 21 st day after operation, the proportion of CD3 + T cells, γδ T cells, CD4 + Tregs and Tregs/Th17 ratio were obviously higher than that of sham operation group. Meanwhile, while CD4 + T cells and CD8 + T cells were lower, suggesting the happen of peripheral immunosuppression. Comparing the T lymphocytes subsets on the 14 th and 21 st day after modeling in the tumor group, it was found that CD3 + T cells and CD4 + Tregs on the 21 st day after modeling were significantly higher than those on the 14 th day while CD4 + T cells, CD8 + T cells decreased significantly, indicating the changes of T lymphocytes in peripheral blood of OS mice are related to tumor development. Conclusions The formation and development of femoral OS is accompanied by the disorder of peripheral blood T lymphocyte subsets and peripheral immunosuppression.

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CD8 T cell–Derived Perforin and TNF-α Are Crucial Mediators of Neuronal Destruction in Experimental Autoimmune Enteric Ganglionitis

Cited by 7 publications

References 45 publications

Levetiracetam Attenuates the Spinal Cord Injury Induced by Acute Trauma via Suppressing the Expression of Perforin

Levetiracetam Attenuates the Spinal Cord Injury Induced by Acute Trauma via Suppressing the Expression of Perforin

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Characteristics and significance of T lymphocyte subsets in peripheral blood of osteosarcoma mice

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