Original Article
Amir Kahrizi; Armin Akbar; Ahmad Najafi; Hossein Asgarian-Omran; Hossein Karami; Mohammad Naderisorki; Alireza Karimi; Mohsen Tehrani
Abstract
Background: Glucose deprivation in T lymphocytes can trigger compensatory metabolic pathways, potentially contributing to T-cell exhaustion. Additionally, it may induce the unfolded protein response (UPR), ultimately resulting in endoplasmic reticulum (ER) stress.Objectives: To examine the transcriptional ...
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Background: Glucose deprivation in T lymphocytes can trigger compensatory metabolic pathways, potentially contributing to T-cell exhaustion. Additionally, it may induce the unfolded protein response (UPR), ultimately resulting in endoplasmic reticulum (ER) stress.Objectives: To examine the transcriptional profiles of endoplasmic reticulum (ER) stress markers and T-cell exhaustion indicators in CD8+ T lymphocytes isolated from B-ALL patients.Methods: Peripheral blood samples were collected from 22 untreated B-ALL patients and 22 healthy controls. Magnetic Activated Cell Sorting (MACS) was used to isolate CD8+ T lymphocytes. The relative gene expression was then assessed using qRT-PCR with primers specific to XBP1, CHOP, GLUT1, and T-bet.Result: The ER stress response was significantly activated in CD8+ T lymphocytes from B-ALL patients, as evidenced by significant increase in both XBP1 and CHOP transcript levels, relative to normal donors. Although GLUT1 mRNA expression was significantly higher than in control groups, T-bet expression showed no significant difference between the two groups..Conclusion: Collectively, our gene expression data suggest ER stress activation in CD8+ T lymphocytes from B-ALL patients. These findings warrant further investigation into ER stress-related signaling pathways and their potential role in promoting T-cell exhaustion in B-ALL.
Original Article
Fariba Akbari Gavabari; Mohsen Rastegari-Pouyani; Saied Afshar; Mehrdokht Mazdeh; Elaheh Talebi-ghane; Mohammad Mahdi Eftekharian
Abstract
Background: Parkinson’s disease (PD) is increasingly recognized as a condition driven by both central and peripheral inflammatory responses, largely mediated by cytokine activity.
Objective: To assess IL-35 (P35 and Ebi3 subunits) and IL-37 gene expression, along with the serum levels of IL-35 ...
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Background: Parkinson’s disease (PD) is increasingly recognized as a condition driven by both central and peripheral inflammatory responses, largely mediated by cytokine activity.
Objective: To assess IL-35 (P35 and Ebi3 subunits) and IL-37 gene expression, along with the serum levels of IL-35 protein in patients with PD compared to healthy controls.
Methods: Cytokine gene expression was measured using the qRT-PCR technique, while IL-35 serum levels were measured using the ELISA method. The data obtained were analyzed using a Bayesian regression model in the R software.
Results: The results revealed that the expression of P35 gene, of the two subunits of IL-35, did not differ significantly between the two groups. However, Ebi3 and IL-37 transcript levels were significantly lower in patients compared to healthy individuals (p<0.001). In contrast, IL-35 serum level in patients showed a significant increase compared to the control group (p=0.016). Notably, IL-37 expression showed a negative correlation with age (p=0.004). . We also observed positive and significant correlations between the gene expression of P35 and Ebi3 (p= 0.02, r= 0.4), P35 and IL-37 (p= 0.008, r= 0.45), and Ebi3 and IL-37 (p= 0.016, r= 0.41).
Conclusion: In conclusion, our study revealed a higher serum protein level of IL-35 in PD patients compared to the healthy control group. Meanwhile, gene expression levels of IL-37 and Ebi-3 were significantly reduced. These alterations in the expression of these cytokines are suggested to be partly responsible for the immune system dysregulation in this disease.
Original Article
Dariush Haghmorad; Arman Rahimmi; Alireza Pazoki; Fatemeh Namazi; Mohammad Reza Rahmani; Abbas Ali Amini
Abstract
Background: Interferon-b (IFN-β), a glycoprotein released during viral infections, plays a crucial role in modulating T cells involved in multiple sclerosis (MS). CD200 is an immunomodulatory molecule expressed in many cell types, including neurons. It reduces the progression of MS and experimental ...
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Background: Interferon-b (IFN-β), a glycoprotein released during viral infections, plays a crucial role in modulating T cells involved in multiple sclerosis (MS). CD200 is an immunomodulatory molecule expressed in many cell types, including neurons. It reduces the progression of MS and experimental autoimmune encephalomyelitis (EAE) by interacting with CD200R, mainly expressed on myeloid lineage cells. This interaction prevents brain damage and slows the progression of the disease.
Objective: This study investigated changes in the expression of CD200 and CD200R genes in the brains of mice induced with EAE.
Methods: Female C57B/L6 mice were divided into three distinct groups: 1) EAE-induced and treated with IFN-b, 2) EAE-induced and treated with phosphate-buffered saline (PBS), and 3) a healthy control group. Two weeks after treatment, the mice were euthanized, and whole-brain tissues were used for mRNA extraction. After cDNA synthesis, the expression of CD200 and CD200R genes was evaluated using Taqman Real-Time PCR. Leukocyte infiltration and demyelination were assessed using Hematoxylin and Eosin staining (H&E) as well as Luxol fast blue (LFB).
Results: IFN-β treatment significantly reduced disease progression and demyelination. Furthermore, mice treated with IFN-β showed improved weight gain. The findings also indicated no notable change in CD200 gene expression across the groups examined. However, the expression of CD200R decreased in the IFN-β-treated group, but significantly increased in the untreated group.
Conclusion: Our findings suggest that IFN-β treatment may decrease CD200R expression by reducing inflammation. Additionally, the elevated expression in the untreated group may explain why EAE is self-limiting.
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