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
Shengnan Xu; Chaoqiong Ye; Zhihua Wu; Chuying Wen; Wenhui Huang; Cong Deng; Jiaye Hua; Wei Xie; Min Xiao
Abstract
Background: Severe neutropenia significantly increases the risk of bacterial infections. Recent studies have shown that the cytokine interleukin 14 (IL-14) plays an important role in immune cells, but its potential role in neutropenia induced by cytarabine (ara-c) or irradiation is unclear.Objective: ...
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Background: Severe neutropenia significantly increases the risk of bacterial infections. Recent studies have shown that the cytokine interleukin 14 (IL-14) plays an important role in immune cells, but its potential role in neutropenia induced by cytarabine (ara-c) or irradiation is unclear.Objective: To investigate the role of IL-14 in ara-c or irradiation-induced neutropenia.Methods: Two neutropenia models were induced by ara-c or irradiation. Neutrophil count was confirmed through flow cytometry and routine blood tests. IL-14 was used to assess the impact on neutropenia. IL-14 expression was analyzed using qPCR, Western blotting and ELISA. A IL-14 receptor (IL-14R) knockout mice model was utilized to confirm the role of IL-14R/STAT3 signaling in vivo.Results: The results indicated that IL-14 treatment promoted proliferation and increased neutrophil counts in both bone marrow and peripheral blood, while IL-14R knockout suppressed this process. Furthermore, the downstream molecule of IL-14R, STAT3, showed enhanced phosphorylation levels in the presence of IL-14. Finally, we explored the source of IL-14 in the bone marrow, and found that lymphocytes secreted the highest levels of IL-14. Serum levels of IL-14 were significantly reduced in patients after chemotherapy.Conclusions: These results indicate that IL-14 prevents ara-c or irradiation-induced neutropenia by regulating lymphocytes and activating the IL-14R/STAT3 pathway in neutrophils. This evidence suggests that IL-14 is a potent cytokine for treating ara-c or irradiation-induced neutropenia.
Original Article
Hongmei Shao; Junjie Chen
Abstract
Background: Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. In this study, we investigated the effectiveness ...
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Background: Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. In this study, we investigated the effectiveness of extracellular vesicles (EVs) derived from MSCs that were genetically modified to overexpress miR-146a, in a mouse model of psoriasis.Methods: To enhance miR-146a expression, MSCs were transfected, and their EVs were subsequently purified. Thirty mice were randomly assigned to three groups and induced with imiquimod cream to develop psoriasis-like skin lesions. The treatment groups included: (1) a control group administered PBS, (2) a group treated with EVs containing a control miRNA (miR-control EVs), and (3) a group receiving EVs enriched with miR-146a (miR-146a-EVs). EVs were administered intravenously and lesions were evaluated. Following intravenous administration of EVs, the severity of skin lesions was assessed. Concentrations of key cytokines, including IFN-γ, IL-17, TNF-α, IL-23, IL-6, IL-1β, TGF-β, IL-10, and IL-4, were quantified in both spleen and skin tissue lysates using ELISA and qRT-PCR techniques.Results: The experimental findings demonstrated that the administration of miR-146a-enriched EVs led to a significant improvement in clinical symptoms. There were substantial reductions observed in combined erythema, scaling, and skin thickness measurements compared to untreated controls. Additionally, levels of proinflammatory cytokines IFN-γ, IL-17, TNF-α, IL-23, IL-6, and IL-1β were significantly downregulated in the miR-146a-EV group, while anti-inflammatory TGF-β, IL-10 and IL-4 were upregulated. The same results were obtained in the spleens of mice.Conclusion: EVs derived from miR-146a-modified MSCs effectively reduced psoriasis-like inflammation by modulating cytokine expression. This novel cell-free therapy holds promise for the treatment of psoriasis.
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.
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 protein ...
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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
Esmat Rigi Yousefabadi; Zahra Ourang; Farhad Gharibdoost; Seyedeh Tahereh Faezi; Mohammad Saatchi; Delnya Gholami; Emran Esmaeilzadeh; Hamid Reza Khorram Khorshid
Abstract
Background: DNA methylation plays a key role in systemic lupus erythematosus (SLE) by regulating gene expression and impacting immune system functions. In SLE, abnormal DNA methylation patterns can lead to the overexpression of pro-inflammatory genes and downregulation of the regulatory genes, contributing ...
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Background: DNA methylation plays a key role in systemic lupus erythematosus (SLE) by regulating gene expression and impacting immune system functions. In SLE, abnormal DNA methylation patterns can lead to the overexpression of pro-inflammatory genes and downregulation of the regulatory genes, contributing to autoimmunity. This dysregulation can increase susceptibility to SLE. Understanding these methylation changes could help discover new therapeutic strategies for managing SLE.Objective: To evaluate methylation levels of OAS2 and OAS3 in peripheral blood mononuclear cells (PBMCs) in volunteers with SLE were evaluated.Methods: In this case-control study, we collected 207 peripheral blood samples from 102 SLE patients and 105 healthy subjects. After isolating the PBMCs, methylation analysis was performed using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) method.Results: The control group had an average OAS2 methylation percentage of 40.02% ± 24.59%, whereas the SLE group had a significantly lower average of 19.46% ± 21.98%. This finding indicates a significant hypomethylation of OAS2 in the SLE cohort (P<0.001). Additionally, a significant difference was observed in the mean methylation levels of OAS3, with SLE patients exhibiting 14.11% ± 19.50% compared to healthy controls at 25.32% ± 20.82% (P<0.001). Patients with renal damage also showed significantly lower OAS2 methylation levels than SLE individuals without renal damage (P<0.001). Furthermore, a negative connection was found between the OAS2 methylation level and creatinine (r= -0.266, P= 0.007).Conclusion: The pattern of methylation levels observed in OAS2 and OAS3 within PBMCs may provide valuable insights into the mechanisms underlying SLE development.
Case Report
Hulya Kose; Yasin Karali; Sara Sebnem Kilic
Abstract
BLNK deficiency is a subtype of autosomal recessive immune disorders that involves a lack of B cells, agammaglobulinemia, and recurrent infections. We present the case of a 29-year-old Turkish female with BLNK deficiency caused by a novel homozygous CGA > TGA mutation at codon 123 (exon 6) in ...
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BLNK deficiency is a subtype of autosomal recessive immune disorders that involves a lack of B cells, agammaglobulinemia, and recurrent infections. We present the case of a 29-year-old Turkish female with BLNK deficiency caused by a novel homozygous CGA > TGA mutation at codon 123 (exon 6) in the BLNK gene. She developed severe liver failure and rickets at the age of 12. Although BLNK mutations are a rare cause of agammaglobulinemia, it is important to consider them in patients with B-cell deficiency and non-immune involvement.
Letter To The Editor
Reza Jafari; Fariborz Bahrami; Byron Arana; Sima Rafati
Abstract
Professor Farrokh Modabber, a prominent immunologist whose early research laid foundational insights into cellular immunology, passed away on May 31, 2025, at the age of 85. Born in Rasht, Iran, he embarked on an illustrious scientific journey that spanned continents and left a lasting impact on immunology ...
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Professor Farrokh Modabber, a prominent immunologist whose early research laid foundational insights into cellular immunology, passed away on May 31, 2025, at the age of 85. Born in Rasht, Iran, he embarked on an illustrious scientific journey that spanned continents and left a lasting impact on immunology and medical research. After graduating from Alborz High School in 1957 in Tehran, Professor Farrokh Modabber earned his B.A. in Bacteriology (1964) and Ph.D. in Microbiology and Immunology (1968) from University of California, Los Angeles (UCLA). Under Professor Eli Sercarz, his doctoral work in the nascent field of Cellular Immunology led to a pioneering enzyme-based fluorescence method to quantify antigen receptors (published in Science. 1968;159(3817):884–5.). Driven by passion, he pursued a post-doctoral fellowship at Harvard Medical School under immunofluorescence pioneer Professor Albert Hewett Coons, studying thymic antigen-binding cells (published in Science. 1970;170(3962):1102–4.). After his fellowship, he joined Harvard School of Public Health as a Research Fellow and Assistant Professor (until 1982), leaving a legacy of scientific innovation, mentorship, and global health impact. Institutional Legacy in IranProfessor Modabber returned to Iran first as Associate Professor at Pahlavi Medical School (now Shiraz University of Medical Sciences) in the Department of Microbiology, (1971-72) and then at Tehran University, School of Public Health in 1973 as Head of Pathobiology Department. There, he established a joint Master's program with Harvard School of Public Health and other top universities that trained generations of Iranian immunologists. His department pioneered Iran's first HLA-typing laboratory, advanced leprosy research, and introduced BALB/c mice for leishmaniasis studies - a model that became globally significant. From 1978 to 1979, as Director General of the Pasteur Institute of Iran, he amicably resolved an international dispute while improving staff welfare and initiating a production complex. Shaping Global Leishmaniases ResearchAfter three years of leishmaniasis research at Institut Pasteur in Paris (1981-1983), Professor Modabber returned to the United States, where aside from lecturing as a Visiting Immunology Professor at multiple universities, he took notable positions with direct impact on leishmaniases research. These included Coordinator of Research Capability Strengthening for the WHO’s Special Programme for Research and Training in Tropical Diseases (TDR) (1984-2000), Director of the Infectious Disease Research Institute (IDRI) (2000-2008), and Senior Advisor to the Drugs for Neglected Diseases Initiative (DNDi) (2008-2025).In his later years, Farrokh devoted himself to DNDi, where he organized and led a research program focused on developing new treatments for Cutaneous Leishmaniasis. The priorities he established laid the foundation for the program’s strategy, and his contributions continue to shape its development to this day. At DNDi, Farrokh was known for his charm, kindness, and exceptional interpersonal skills—qualities that, combined with his brilliant scientific mind, became his hallmark.Scientific MilestonesProfessor Modabber has made substantial contributions across various domains:1. More than 84 publications (H-index 38).2. Leishmania Persistence: Professor Modabber was a pioneer in understanding the long-term persistence of Leishmania parasites in hosts, even after clinical cure. His research helped explain why recovered individuals have long-lasting immunity and HIV infection triggers relapse of parasites.3. Vaccine Development: He established the BALB/c challenge model and developed killed-parasite vaccines in conjunction with Bacillus Calmette-Guérin (BCG).4. Global Policy: He played a pivotal role in shaping World Health Organization (WHO) guidelines during his tenure as the coordinator for the Tropical Diseases Research (TDR) program from 1990 to 1996.5. Technology Transfer: He was a key figure in the introduction of flow cytometry to Iran in 1982.6. The WHO's adoption of the "Modabber Protocol" for post-kala-azar dermal leishmaniasis (PKDL) treatment. Professor Modabber is survived by his wife, Marlies Haegglund, an Austrian colleague from the WHO, and his daughter, Yalda, Founder and Executive Director of Golestan School in Berkeley, California, as well as his sons, Zia, a prominent lawyer in Los Angeles; Ramin, a distinguished orthopedic surgeon and mentor in Santa Monica; and Nader, an accomplished artist in Santa Monica. He was preceded in death by his second wife, Minou Bayat-Modabber, and was previously married to Lillian Guttman-Roth in 1961.
