Iranian Journal of Allergy, Asthma and Immunology

Cracking the Human Cytomegalovirus Code: Trinary Challenges of Latency, Immune Evasion, and Correlates of Protection

Somayeh Mami — 2025-07-19

Human cytomegalovirus (HCMV) poses a significant challenge to vaccine development due to its complex biology characterized by latency, immune evasion strategies, and undefined correlates of protection (CoPs). HCMV latency allows the virus to evade immune surveillance by remaining in a quiescent state in host cells, with the risk of reactivation triggered by immune damage or cell differentiation. In addition, HCMV employs an arsenal of immune evasion strategies, including modulating MHC expression, inhibiting natural killer (NK) cell activity, and subverting antibody-mediated responses, so these mechanisms further complicate vaccine design. Despite these obstacles, advances in basic research in immunology and vaccine technologies offer new opportunities. Strategies such as targeting latency-associated mechanisms, using memory inflation of CMV-specific T cells to induce long-term tissue-resident immunity, and developing immunogens that antagonize viral immunoevasins are promising approaches. New platforms, including mRNA and vector-based vaccines, show the potential to elicit robust humoral and cellular responses against key viral antigens such as glycoprotein B, pentamer complex, and pp65. In addition, adjuvants that restore impaired NK and T cell function could improve vaccine effectiveness. This review examines the molecular and immunological barriers to HCMV vaccine development and highlights innovative approaches to address these challenges. By addressing the complexities of latency, immune evasion, and CoPs, we propose a roadmap for developing a multimodal vaccine that can provide effective and durable protection against HCMV infections.

Exercise and Immune System: A Comprehensive Review in the Era of COVID-19 Outbreak

Sahar Rahimi — 2025-07-19

The COVID-19 pandemic has highlighted the essential role of a strong immune system in fighting infectious diseases. Understanding the relationship between exercise, physical activity, and immune function is crucial for recognizing how lifestyle factors can improve immune resilience. This review article aims to provide a comprehensive overview of the effects of exercise on the immune system during the COVID-19 pandemic. Additionally, it presents recommendations, guidelines, and considerations for engaging in physical activity during this period. Based on the literature review, there is some controversy regarding the effects of high-intensity exercise on individuals' immune systems, whereas moderate exercise is generally beneficial in almost all cases. Also, individuals experiencing severe COVID-19 symptoms or other acute illnesses should abstain from physical activity until recovery.

Evaluating the Role of Fractional Exhaled Nitric Oxide (FeNO) and Inflammatory Biomarkers in Diagnosing Non-Chronic Cough in Pediatric Patients: A Cross-Sectional Study

Soheila Alyasin — 2025-07-19

Fractional exhaled nitric oxide (FeNO) has emerged as a potential biomarker for differentiating between various causes of non-chronic cough, particularly in conditions associated with airway inflammation, such as asthma. This study aimed to evaluate the diagnostic efficacy of FeNO in pediatric patients with non-chronic cough and its ability to differentiate between asthma exacerbations and respiratory tract infections.

Seventy-five pediatric patients aged 10-18 years with non-chronic cough were categorized into three groups: good control asthma (GCA, n=28), acute asthma exacerbation (AAE, n=26), and respiratory tract infection (RTI, n=21). Clinical assessments included FeNO measurement, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), and immunoglobulin E (IgE) levels. Univariate and multivariate multinomial logistic regression models were applied to assess the predictive value of these variables.

FeNO levels were significantly higher in the AAE group (46.58±22.66 ppb) compared to the GCA and RTI groups, indicating elevated eosinophilic airway inflammation in asthma exacerbations. CRP was a significant predictor of both AAE and RTI, with a one-unit increase in CRP increasing the odds of exacerbation or infection by 2.6-fold. Body max index (BMI) was inversely associated with the risk of RTI. Hemoglobin, platelet count, and IgE levels were significantly higher in the AAE group compared to the other groups, while WBC counts, though elevated, were not statistically significant.

FeNO associated with other inflammatory markers, including CRP and BMI, could enhance diagnostic accuracy and inform clinical decision-making in managing pediatric respiratory conditions. To confirm these results, future studies with larger sample sizes should be performed.

Clinical Characteristics and Predictive Factors Analysis of Mycoplasma Pneumoniae Pneumonia Complicated with Pleural Effusion in Children

Lianlian Ji — 2025-07-19

Mycoplasma pneumoniae pneumonia (MPP) is a prevalent cause of respiratory infections in children, sometimes leading to pleural effusion (PE). This study aimed to identify risk factors and clinical features associated with PE in pediatric MPP patients.

We conducted a retrospective case-control study involving 412 children with MPP and 82 with MPP+PE at the Third Affiliated Hospital of Wenzhou Medical University from January 2021 to January 2024. Demographic, clinical, and laboratory data were analyzed using multivariate logistic regression and receiver operating characteristic (ROC) curves.

Significant findings included a higher incidence of immunocompromised states in the MPP+PE group (18.29% vs. 8.98%). At admission, children with MPP+PE exhibited higher respiratory rates (29.94 vs. 29.16 breaths/min), lower oxygen saturation (82.33% vs. 83.14%), longer fever duration (5.75 vs. 4.83 days), elevated white blood cell counts (WBC) (11.64×10^9/L vs. 10.12×10^9/L), and increased erythrocyte sedimentation rates (ESR) (20.66 vs. 19.49 mm/h). Patients with PE also experienced longer antibiotic treatment (9.14±4.91 vs. 7.46±3.29 days) and extended hospital stays (13.58±4.18 vs. 12.37±3.52 days). Multivariate analysis identified several significant predictors of PE, and a joint prediction model achieved an area under the curve (AUC) of 0.842, sensitivity of 0.796, and specificity of 0.793.

These findings suggest that specific clinical and laboratory factors can help identify children at higher risk for PE, facilitating timely interventions.

Predictive Value of Peripheral Blood Follicular Helper T Cells for Short-term Prognosis in Patients with Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors

Yihao Lin — 2025-07-19

Peripheral blood follicular helper T cells (Tfh) are essential in humoral immunity; however, their prognostic significance in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) is not well understood. This study aimed to evaluate the predictive value of Tfh cells for short-term prognosis in 200 HCC patients undergoing ICIs.

A retrospective analysis categorized patients based on their clinical outcomes at six months post-treatment: those demonstrating improvement were classified as having a favorable prognosis (n=86), while those with no remission, deterioration, or death were classified as having a poor prognosis (n=114). Key prognostic factors assessed included C-reactive protein (CRP), interleukin-6 (IL-6), Tfh cell counts, and combination therapy.

Significant associations were identified between prognosis and CRP, IL-6, Tfh cell counts, and combination therapy. Multivariate analysis revealed these factors as independent predictors of short-term prognosis, explaining 78.3% of the variance. The area under the curve (AUC) for Tfh cells was 0.902 (95% CI: 0.8567-0.9477), with 100% sensitivity and 80.70% specificity at a cut-off of 1.995. Patients with elevated Tfh levels (≥1.995, n=93) had a median overall survival (OS) of 5 months, significantly earlier than those with lower levels (<1.995, n=107), whose median OS was not reached.

Tfh cells are independent predictors of short-term prognosis in HCC patients receiving ICIs. Reduced Tfh levels correlate with improved outcomes, providing crucial insights for clinical decision-making.

The Relationship between Autophagy Process and Expression of MicroRNA-146a-5p in MKN-45 and MCF-7 Cell Lines

Atefe Alirezaee — 2025-07-19

After chemotherapy or radiation therapy, autophagy activity increases in tumor cells for the adaptation of the tumor cells to stress. Thus, disturbance in autophagy can enhance the effectiveness of anticancer drugs. On the other hand, recent findings highlight the importance of microRNAs (miRs) in autophagy, including miR-146a-5p. In gastric and breast cancer miR-146a-5p is frequently reduced, and more precise identification of its function in these cancers is needed. The aim of this study was to evaluate the relationship between miR-146a-5p and autophagy in MKN-45 (human stomach cancer cell line) and MCF-7(breast cancer cell line).

The expression of miR-146a-5p in MKN-45 and MCF-7 cell lines was measured before
and after induction of autophagy using real-time polymerase chain reaction (PCR). A flow cytometry assay was used for the apoptosis assay, and autophagy induction was approved. Also, the
formation of autophagic vacuoles was ensured in cells by western blotting and fluorescence microscopy.

Real-time PCR showed that miR-146a-5p level in starvation groups, during autophagy, was significantly lower than in control groups, and also tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) level, a key target of miR-146a-5p, in starvation groups, during autophagy, was more than control groups but it was significant only in the MCF-7 group.

According to previous studies and the results of the present study, miR-146a-5p may be considered a negative regulator of autophagy. However, to confirm this, further studies are needed on different cancer cell lines.

MicroRNA-148a-3p Regulates Colorectal Cancer Cell Proliferation and Immune Escape through KLF4

Chunlei Zhang — 2025-07-19

MicroRNA (miR)-148a-3p is most frequently upregulated in solid tumors, such as colorectalcancer (CRC). This study aimed to elucidate the role of miR-148a-3p in CRC cell proliferation andimmune escape and its potential mechanism.miR-148a-3p and Kruppel-like transcription factor 4 (KLF4) expressions were quantified bywestern blot and quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation,migration, invasion, epithelial-mesenchymal transition (EMT), and immune evasion abilities of CRCcells were evaluated with the cell counting kit-8 assay, Transwell, western blot, and enzyme-linkedimmunosorbent assays. The proliferation or apoptosis of CD8+ and CD4+ T cells after coculturewith CRC cells was assessed by flow cytometry. Dual-luciferase reporter gene testing was used tovalidate the targeting association between KLF4 and miR-148a-3p. A nude mouse subcutaneousgraft tumor model was constructed, and CD8+ T cell infiltration was detected byimmunohistochemistry and flow cytometry.miR-148a-3p exhibited a high level, while KLF4 was under-expressed in CRC cells; miR-148a-3p negatively regulated the KLF4 level. Overexpression of miR-148a-3p enhanced CRC cellproliferation, migration, invasion, EMT, and immune escape; silencing miR-148a-3p caused theopposite trend; moreover, the said biological functions of CRC cells were weakened withoverexpression of KLF4 but enhanced with silencing of KLF4; silencing KLF4 weakened theinfluences of dampened miR-148a-3p on CRC development. Silencing miR-148a-3p promoted theinfiltration of CD8+ T cells and inhibited tumor growth.In summary, miR-148a-3p promotes CRC cell proliferation and immune evasion by regulatingthe expression of KLF4. This finding can be used for reference when developing a new way of CRCtreatment.

The Antitumor Effect of a Non-Transforming E7 Protein Combined with a TLR7 Agonist

Maryam Mashhadi Abolghasem Shirazi — 2025-07-19

Despite great efforts in developing peptide-based therapeutic vaccines against human papillomavirus (HPV)-induced cervical cancers, they have failed to elicit strong and sustainable immune responses. Here, we evaluated the vaccine potential of an HPV16 three mutant of E7 (E7GGG) (D21G/C24G/E26G) protein combined with Aldara (topical imiquimod) adjuvant in a TC-1 mouse tumor model.

The HPV16-E7GGG, with eliminated transforming properties but retained antigenicity, and E7 wild-type were inserted into pET28, expressed in the E coli system, and purified using Ni-NTA chromatography. The E7GGG and E7 wild-type proteins were combined with Aldara adjuvant and injected into C57BL mice.

We determined the ability of HPV16-E7GGG in combination with Aldara adjuvant to induce robust immune responses by IgG total development, IL-4, IL-17, and IFN-γ induction, CTL activity, and inhibit tumor growth in the murine TC-1 model in different immunized groups.

The generated recombinant HPV16-E7GGG induced humoral and cellular immune responses in a T_H1-mediated pathway, specifically with the (E7GGG) (D21G/C24G/E26G) antigen combined with Aldara, which could be a suitable therapeutic vaccine candidate against HPV.

Effects of Hypoxia in Pancreatic Cancer on Immune Cell Behavior in the Tumor Microenvironment

Xiaojun Wen — 2025-07-19

Hypoxia serves as a fundamental component of the tumor microenvironment, exerting a crucial influence on tumor advancement. Nonetheless, a comprehensive examination of a prognostic signature linked to hypoxia in pancreatic cancer is notably absent, presenting an urgent necessity. Therefore, our objective was to create and authenticate a robust prognostic signature capable of predicting outcomes for pancreatic cancer.

Initially, the Gene Set Enrichment Analysis (GSEA) database was used to obtain hypoxia-related genes, and prognostic genes were analyzed. Following this, we utilized the Lasso Cox regression model to construct the hypoxia risk score model. Pancreatic cancer patients were subsequently categorized into high- and low-risk groups according to the median risk score. Finally, the CIBERSORT technique was used to assess immune cell infiltration while examining the relationship between hypoxia and immune-related genes.

Applying the Lasso Cox regression model, we pinpointed 2 significant genes, GYS1 and ALDOB. Following this, patients were categorized into hypoxia high-risk and low-risk groups. Notably, the low-risk cohort demonstrated a substantially heightened survival rate relative to the high-risk group. Further investigation into the immune microenvironment unveiled a greater prevalence of resting mast cells, monocytes, plasma cells, and naive CD4⁺ T cells in the low-risk category. In addition, we detected differences in the expression of 39 immune-related genes between the 2 groups.

In summary, our study has established a predictive signature comprising molecular markers for forecasting the prognosis of pancreatic cancer patients.

Immune Landscape and Prognostic Significance of Gene Expression Profiles in Bladder Cancer: Insights from Immune Cell Infiltration and Risk Modeling

Ye Zhou — 2025-07-19

To explore the immunological underpinnings and prognostic potential of gene expression profiles in bladder cancer through comprehensive analyses of The Cancer Genome Atlas (TCGA) data.

We used the TCGA data to identify differentially expressed genes (DEGs) and performed enrichment analysis to reveal the related biological pathways. Meanwhile, the least absolute shrinkage and selection operator (LASSO) algorithm was adopted to develop a prognostic model. Then we evaluated the performance of the model in both TCGA and GSE13507 datasets. Furthermore, we conducted a comprehensive investigation on the feature genes utilized in model construction, encompassing both gene expression profiling and survival analysis. Finally, immune infiltration analysis and drug sensitivity analysis were applied to elucidate the immunological basis of the disease and provide potential therapeutic strategies.

We identified a total of 837 DEGs, with a focus on immune-related genes. Using the LASSO algorithm, we developed a prognostic model incorporating seven key genes—NXPH4, FAM110B, GPC2, STXBP6, CYP27B1, GARNL3, and PTGER3—which demonstrated strong predictive accuracy in both TCGA and GSE13507 datasets. Moreover, immune infiltration analysis revealed a higher abundance of M0 and M2 macrophages in high-risk patients, suggesting that macrophage polarization could be a potential therapeutic target to modulate the immune microenvironment. Drug sensitivity analysis further suggested that high-risk patients exhibit differential responses to several chemotherapy agents, with potential therapeutic implications.

This study constructed an effective prognostic model, providing new insights and potential therapeutic targets for the personalized treatment of bladder cancer, which needs further validation.

Interleukin-17 Receptor Signaling Regulates Immune Response and Slows Down Myocardial Fibrosis in Mice with Dilated Cardiomyopath

Weiwei Li — 2025-07-19

Immune response is a significant mechanism in dilated cardiomyopathy (DCM). The interleukin-17 receptor (IL-17R) is crucial for immune response. A DCM model was created using doxorubicin, and IL-17R was knocked down. We assessed cardiac function, histopathological changes, fibrosis proteins, myocardial injury, and inflammation levels through echocardiography, pathological staining, immunofluorescence, and Western blot, respectively. The proportions of T cell subsets in mouse spleen tissue were identified through flow cytometry. Following these steps, we detached fibroblasts from the mouse heart and knocked down IL-17R. Angiotensin II was employed to induce cell fibrosis and co-cultured with T Helper 17 (TH17) cells. We measured inflammation, collagen deposits, and fibrosis protein expression using Sirius red staining, immunofluorescence, and Western blot. IL-17R exhibited significant expression in DCM mice. The systolic function of DCM mice significantly decreased. Myocardial fibrosis and collagen deposition in the left ventricle were markedly elevated. The levels of fibrosis proteins and pro-inflammatory factors were notably enhanced (p < 0.01). The proportion of effector CD4+ T and TH17 cells in spleen tissue noticeably increased, while the Treg cell proportion notably decreased (p < 0.05). These indicators were significantly reversed after IL-17R knockdown. In the co-culture system, pro-inflammatory cytokines, collagen formation, and fibrosis-related protein levels increased significantly after fibrosis induction. However, the level of fibrosis and TH17/Treg cell imbalance decreased significantly after IL-17R knockdown. The knockdown of IL-17R can reduce immune reaction, which in turn improves myocardial fibrosis and alleviates DCM cardiac function

High-dose Vitamin D Supplementation Attenuates NLRP3 Inflammasome-mediated Oxidative Stress in a Novel Murine Model of Comorbid Asthma and Osteoporosis Induced by Vitamin D Deficiency

Pengtao Song — 2025-07-19

While vitamin D deficiency (VDD) is implicated in both asthma and osteoporosis, the synergistic mechanisms linking these comorbidities remain unexplored. This study introduces a novel murine model of VDD-induced concurrent asthma and osteoporosis, uniquely addressing their bidirectional exacerbation through NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and oxidative stress crosstalk. Female C57 mice were stratified into control, bronchial asthma (BA), osteoporosis (OP), BA+OP, and VDD+BA+OP groups, with therapeutic evaluation of low-dose (LD) and high-dose (HD) vitamin D supplementation. Unlike prior studies, our results demonstrate that VDD amplifies airway resistance and bone microstructural deterioration via NLRP3-driven pyroptosis (elevated cleaved caspase-1, N-terminal gasdermin D and suppressed antioxidant defenses (reduced glutathione peroxidase and catalase, and elevated malondialdehyde). Critically, HD supplementation reversed these effects more robustly than LD, restoring pulmonary compliance, trabecular integrity (bone volume/total volume: 0.0298 vs 0.0356 in VDD+BA+OP), and suppressing inflammasome activity. Mechanistically, we identify a feedforward loop wherein VDD-induced oxidative stress primes NLRP3 activation, which further exacerbates inflammation and bone resorption—a pathway uniquely mitigated by HD vitamin D. These findings provide the first evidence of HD vitamin D’s dual therapeutic efficacy in comorbid asthma-osteoporosis, offering a paradigm shift in targeting the NLRP3/oxidative stress axis for managing multifactorial inflammatory diseases.