Iranian Journal of Allergy, Asthma and Immunology

Immunomodulatory Effects of Stem Cell Therapy in Liver Fibrosis: A Systematic Review

Sahar Rahimi — 2025-11-09

Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the management of liver fibrosis because it not only improves tissue regeneration but also modulates by immunomodulatory mechanisms.

This systematic review aimed to evaluate the immunoregulatory effects of stem cells in both experimental models and clinical studies of liver fibrosis. A total of 29 studies were included, comprising several stem cell sources, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (AT-MSCs), and stem cells from human exfoliated deciduous teeth (SHED), among others. Studies reported that stem cells could decrease proinflammatory cytokines (e.g., TNF-α, IFN-γ, IL-17) and fibrosis-related markers, while increasing levels of anti-inflammatory cytokines (e.g., IL-10, IL-4) and regulatory immune cells such as Tregs (regulatory T cells). Stem cells could affect immune homeostasis via modulating in macrophage polarization, T cell subsets, and B cell activity, resulting in attenuated fibrotic progression and improved liver function.

Despite variability in cell types, routes of administration, and fibrosis models, the results support the potential of stem cell therapy to reform the hepatic immune microenvironment. However, more standardized protocols and clinical validations are required.

This study emphasizes the immunomodulatory potential of stem cells as a therapeutic method in liver fibrosis. It brings a clear view into their mechanisms of action and the foundation for future translational applications.

Comparison of Oral Desensitization with Heated Cow's Milk Products with Conventional Desensitization Method in Children with Cow's Milk Allergy

Masoud Movahedi — 2025-11-09

Cow’s milk allergy (CMA) is one of the most prevalent Immunoglobulin E (IgE)-dependent food allergies in children. Currently, the only accepted treatment for food allergy is avoiding the relevant allergen. The purpose of this study is to investigate the immunological changes following the consumption of heated cow's milk products compared to the usual method of oral desensitization in children aged over two years old with cow's milk allergy.

In a prospective double-blind clinical trial study, 25 children aged two years and older
with a definite diagnosis of IgE-dependent cow's milk allergy referred to the allergy clinic of the Children's Medical Center from 2016 to 2017 were enrolled. The eligible patients were randomly divided into two groups: the first group was desensitized with raw milk (normal desensitization: n=13), and the second group was desensitized with heated cow's milk products (intervention group, n=12).

The mean ages in the raw milk group and heated milk group were 3.92±1.44 and 4.50±1.73 years, respectively. The rate of anaphylaxis in the heated milk group was higher than in the raw milk group (50% vs. 15.4%), although the incidence of urticaria and angioedema was not significantly different between the two groups. The mean concentration of serum IgE in the two groups decreased after desensitization compared to before, although there was no significant difference between the two groups. The increase in the number of CD4+Foxp3+ and CD4+ CD25+ cells was less in the heated milk group than the raw milk group, but this difference was not statistically significant. Additionally, the number of eosinophil cells was higher in the heated milk group than in the raw milk group, but this difference was not statistically significant difference.

We concluded that the changes in the level of eosinophil, IgE, and regulatory T cells in the conventional desensitization group were not significantly different compared to desensitization with heated milk. Further multicenter studies with a higher sample size are recommended to confirm these results.

Comparing Basophil Activation Test and Specific IgE Assay in the Diagnosis of Allergy to Penicillin G and Ibuprofen

Parastoo Shakerin — 2025-11-09

The risks associated with in vivo tests in the diagnosis of immediate drug hypersensitivities result in evaluating alternative in vitro tests, such as the Basophil Activation Test (BAT). This pilot study aimed to set up a BAT and compare it with a specific Immunoglobulin E (sIgE) assay for penicillin G and Ibuprofen in patients with immediate hypersensitivity to β-lactams or nonsteroidal anti-inflammatory drugs (NSAIDs).

Eleven subjects with a clear history of immediate hypersensitivity to one of the β-lactams (n=5), the NSAIDs (n=3), or both (n=3) entered this study. BAT and sIgE assays were performed regarding the patient’s history.

The most frequent manifestations were angioedema, shortness of breath, urticaria, and nausea. Eight patients had anaphylactic reactions. The results presented a positive BAT for penicillin G and one for Ibuprofen. Moreover, three patients with a history of the β-lactams reaction demonstrated positive sIgE to β-lactams in the ImmunoCAP. Despite a lack of agreement between the positive results of the BAT and sIgE assay, five patients were identified by one of these methods.

Despite positive BAT and sIgE results in two and three patients, respectively, the risks, high cost, and time-consuming nature of drug challenges render these tests valuable for reducing the number of patients who are candidates for a drug challenge.

Expression of Serum Immune Inflammatory Factors in Children with Suppurative Tonsillitis Caused by Adenovirus Infection and its Correlation with Adenovirus Pneumonia

Dan Lei — 2025-11-09

Adenovirus infection is a common cause of pediatric respiratory disease, often misdiagnosed as a bacterial infection. This study compared immune-inflammatory markers in children with adenovirus- vs bacterial-induced suppurative tonsillitis and evaluated their correlation with adenovirus pneumonia.

A retrospective study of 275 children (145 with adenovirus, 130 with bacterial infections) admitted to The First People’s Hospital of Changde, China (January–June 2019), was conducted. Laboratory markers (white blood cell [WBC] count, C-reactive protein [CRP], serum amyloid A [SAA], procalcitonin [PCT], heparin-binding protein [HBP], tumor necrosis factor-alpha [TNF-α], and interleukin 6 [IL-6]) were analyzed. Adenovirus cases were stratified by pneumonia status (58 with pneumonia, 87 without pneumonia) via chest computed tomography.

Compared with the bacterial group, the adenovirus group had lower WBC counts (14.97 [1.37] vs 18.86 [2.65] ×10⁹/L), CRP levels (15.26 [3.44] vs 26.36 [3.18] mg/L), and PCT levels (15.06 [2.12] vs 42.53 [4.58] ng/L) but higher SAA levels (216.75 [39.23] vs 136.55 [28.66] mg/L). Among children with adenovirus, those with pneumonia had elevated SAA (236.39 [38.67] vs 203.65 [33.95] mg/L), HBP (44.30 [8.93] vs 35.62 [6.77] ng/mL), TNF-α (731.52 [99.21] vs 604.21 [95.53] ng/L), and IL-6 (96.86 [17.63] vs 76.55 [15.50] ng/L) levels. A combination of SAA, HBP, TNF-α, and IL-6 predicted pneumonia with an area under the curve of 0.927 (sensitivity, 87.93%; specificity, 88.51%).

SAA, HBP, TNF-α, and IL-6 are strongly associated with adenovirus pneumonia, and their combined measurement improves diagnostic accuracy.

Relative and Absolute Regulatory T Cells in Preterm Neonates with Necrotizing Enterocolitis

Ying Cheng — 2025-11-09

The objective of this study was to compare the concentrations of relative and absolute regulatory T cells (Tregs) in preterm neonates diagnosed with necrotizing enterocolitis (NEC) with those in the control group.

The study consisted of 60 preterm neonates, 30 with NEC and 30 without NEC. Blood samples were obtained and processed for the enumeration of Treg cells by multiparameter flow cytometry with markers such as CD4, CD25, and FOXP3, and the activation markers CD45RA, CD45RO, HLA-DR, and CTLA-4.

There were no significant differences in gestational age, body weight, Apgar score, delivery mode, or incidence of maternal infection between the NEC group and the control group. The relative Treg percentage (% of CD4⁺ T cells) in the NEC group was 7.5 ± 1.2%, which was significantly lower than that in the control group (9.8 ± 1.5%). Compared with that in the control group, the absolute Treg count in the NEC group showed the same trend, and the total CD4⁺ T-cell count decreased significantly. The percentage of naive Tregs (% of Tregs) was significantly lower, whereas those of memory Tregs (% of Tregs), Ki-67+ (% of Tregs), and CD39⁺ (% of Tregs) cells were significantly higher. Tregs may be activated more as the severity of NEC increases, and the elevated levels of interleukin (IL)-10 in NEC may reflect attempts at an effective anti-inflammatory response to the proinflammatory effects of IL-6 and TNF-ɑ.

Treg pathways may hold promise for NEC prognosis, although additional samples should be evaluated to validate these results.

Relationship between the Effects of Different Parenteral Nutrition Durations of Two Intravenous Fat Emulsions on Intravenous Nutrition-related Immune Status and Clinical Outcomes in Premature Infants

Lin Yao — 2025-11-09

Premature infants with immature gastrointestinal tracts rely on parenteral nutrition (PN) to meet nutritional and energy requirements for growth. In this study, we compared the nutrition-related immune status of premature infants receiving SMOF emulsions (multiple oil-fat emulsions) versus those receiving MCT/LCT emulsions (medium-/long-chain triglyceride emulsions) at different times during PN, and we analyzed the relationship between immune function and clinical outcomes.

Sixty premature infants from Dongxihu District People’s Hospital, recruited between September 2023 and September 2024, were divided into an observation group and a control group. The observation group received SMOF emulsions, while the control group received MCT/LCT-containing emulsions. We compared immune function, clinical outcomes, and complications between the two groups at different PN timings. The effects of fat-emulsion type on immune indices and their relationship with clinical outcomes were assessed using logistic regression and ROC analysis.

The clinical data of the preterm infants in both groups were similar. Immune function and clinical outcomes were better in the observation group than in the control group, and the complication rate was lower. Logistic and ROC analyses revealed that the type of fat emulsion was closely related to immune indices, and these immune indices were highly correlated with clinical outcomes.

Both interventions improved immunity in preterm infants, with better results in the observation group than in the control group. The use of SMOF emulsions was superior to MCT/LCT-containing emulsions in preterm infants requiring long-term PN, and this immune improvement significantly optimizes clinical outcomes.

Transcription Factor and Cytokine Profiles in Peripheral Blood T Helper Cells in Patients with Idiopathic Pulmonary Fibrosis

Neda Dalil Roofchayee — 2025-11-09

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a poor prognosis, characterized by immune cell activation. The role of T helper (Th) cell transcription factors in IPF pathogenesis remains unclear. In this study, we investigated Th cell transcription factors and related cytokines in IPF patients.

Twelve IPF patients and eight healthy controls (HC) were enrolled in this pilot study. Serum levels of fibrosis-associated mediators (Interferon-inducible protein 10 (IP-10), tumor necrosis factor-α (TNF-α), tumor growth factor-β (TGF-β), CXCL-8, interferon-γ (IFN-γ)) were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed Th transcription factors T box transcription factor (T-bet,), GATA-binding protein 3 (GATA-3), Retinoic acid-related orphan recepto (ROR-γt), forkhead box P3 (FOXP3)) and intracellular cytokines (IL-4, IL-17).

SerumTGF-β, CXCL-8, TNF-α, and IFN-γ were significantly elevated, while IP-10 (pT-bet, GATA3, ROR-γt, or FOXP3 were observed. Positive correlations were found between T-bet and GATA3, IL-4, ROR-γt, and TNF-α expression with age, while FOXP3 expression negatively correlated with age.

T-cell transcription factors were unchanged in IPF despite changes in inflammatory protein expression. Reduced IP-10 may serve as a potential marker.

Measuring Dedicator of Cytokinesis 8 (DOCK8) Expression as a Flow Cytometry Biomarker for DOCK8 Deficiency Detection

Maryam Moradi — 2025-11-09

The autosomal recessive form of hyperimmunoglobulin E syndrome (AR-HIES), caused by mutations in the DOCK8 (Dedicator of Cytokinesis 8) gene, presents a wide range of clinical manifestations and phenotypically overlaps with several types of combined immunodeficiency disorders characterized by elevated serum IgE levels. Due to the high rates of morbidity and mortality, as well as the potential curability through hematopoietic stem cell transplantation (HSCT), early and accurate differential diagnosis of this syndrome is crucial for optimal management and improved prognosis. Flow cytometry tests can be beneficial for early diagnosis of many inborn errors of immunity (IEIs), including this syndrome. This study, conducted for the first time on Iranian patients, investigated the expression of the DOCK8 protein.

DOCK8 expression was assessed by flow cytometry in 14 patients (6 males and 8 females) with
a clinical diagnosis of DOCK8 deficiency. The diagnosis was ultimately confirmed through genetic
testing.

The results showed that DOCK8 expression in patients was significantly lower compared to the healthy control group.

Flow cytometric evaluation of DOCK8 protein expression offers a rapid and efficient
diagnostic method with a sensitive detection range suitable for many cases. This approach can facilitate the diagnosis of DOCK8 deficiency, thereby enabling timely and effective disease management.

Investigating Novel Biomarkers in Endometrial Cancer: A Study on RT-qPCR and Immunohistochemistry

Rong Li — 2025-11-09

This study aimed to investigate the expression patterns of HOXB9, DLX5, NGR1, and GATA6 in endometrial cancer tissues compared to adjacent non-cancerous tissues.

Using RT-qPCR and immunohistochemistry, the researchers found significant upregulation of HOXB9, DLX5, and NGR1, and downregulation of GATA6 in endometrial cancer samples.

The biomarker expression levels correlated with clinicopathological features, and survival analysis revealed that high expression of HOXB9, DLX5, and NGR1 was associated with poorer prognosis, while high GATA6 expression indicated better outcomes.

These findings suggest that these biomarkers may play crucial roles in endometrial cancer development and progression, highlighting their potential as diagnostic, prognostic, and therapeutic targets.

Abscisic Acid Regulates Immune-inflammatory Responses to Induce Neuroprotection in Spinal Cord Injury: Insights from Gene Expression and Network Analysis

Maryam Rezaeezadeh_Roukerd — 2025-11-09

Spinal cord injuries (SCI) lead to complex primary and secondary damage that disrupts neural function. Current treatments are often insufficient and unable to fully repair spinal cord injuries, highlighting the urgent need for new medicines and innovative therapies.

This study aimed to evaluate the therapeutic potential of abscisic acid (ABA) in SCI by examining its effects on immune-inflammatory genes’ expression in rats. This phytohormone possesses anti-inflammatory and neuroprotective properties, rendering it a potential agent for reducing secondary damage following spinal cord injury. Additionally, we performed protein-protein interaction (PPI), pathway enrichment, functional annotation, and gene ontology (GO) analyses to gain a comprehensive understanding of the functions of the affected genes.

Based on the results, SCI led to changes in the expression of immune/inflammation-related genes in rats. However, the administration of ABA alleviated the effects. ABA downregulated proinflammatory genes (IL-6, IL-1β, MCP, TLR2, TLR4) and neural signaling components (NMDA, AMPA, NK1R), while upregulating adrenergic receptors (ADRA1A, ADRB1) and a gamma-aminobutyric acid receptor (AGBRA2). PPI analysis identified FOS, IL-1β, IL-6, MMP9, and TLR4 as crucial nodes in the network, exhibiting the highest degree of interaction. Functional analyses revealed potential impacts on cellular responses, metabolic processes, and synapse-associated extracellular matrix components. Notably, these genes were enriched in inflammatory signaling pathways according to KEGG analysis.

These findings suggest that ABA has a significant modulatory effect on gene expression following SCI, particularly in reducing inflammation and immune responses, thereby highlighting its potential as a novel therapeutic agent for SCI.

MiR-425-5p Mediation of Malignant Behavior and Immune Escape of Cervical Cancer Cells by Targeting NCAM1

Mi Xiang — 2025-11-09

MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells.

The levels of neural cell adhesion molecule 1 (NCAM1) and miR-425-5p in CxCa tissues and cells were tested using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests. CxCa cells’ malignant phenotype was examined through clone formation tests, and transwell tests. CD8+T cells were co-cultured with CxCa cells and then analyzed for apoptosis rates and the expression of activation proteins (granzyme B (GZMB) and perforin) as well as immune factors (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) using flow cytometry, western blot, and enzyme-linked immunosorbent assay (ELISA) methods. Finally, in nude mouse experiments, the tumor size was measured for subcutaneous tumors, and the expression of CD8+T cell-related factors was detected.

The NCAM1 and miR-425-5p were down-regulated and up-regulated in CxCa tissue and cells, respectively. After silencing miR-425-5p, CxCa cells showed attenuation in vitality, clone formation rate, and their capacities to migrate, penetrate, and evade immune responses. NCAM1 was targeted and silenced by miR-425-5p. When NCAM1 was silenced, it partially counteracted miR-425-5p’s inhibitory effects on the immune escape and proliferation. In nude mice, the tumor size and weight decreased after silencing miR-425-5p, and levels of CD8, IFN-γ, TNF-α, perforin, and GZMB were elevated. However, these changes were reversed when NCAM1 was silenced.

In conclusion, miR-425-5p mediates the biological behavior and immune evasion of CxCa cells by regulating NCAM1.

The Mechanism of Notopterol Alleviating LPS-induced Endometritis by Inhibiting the TLR4/NF-κB Signaling Pathway

Zhaomei Xu — 2025-11-09

This study aims to investigate the role of notopterol in alleviating endometritis induced by lipopolysaccharide (LPS) and to explore its underlying mechanisms.Human endometrial epithelial cells (hEECs) were treated with LPS to establish an in vitro model of endometritis, and the cells were divided into five groups: control, LPS, LPS+notopterol(15 mol/L), LPS+notopterol(305 mol/L) and LPS+notopterol(45 mol/L) groups. The expression levels of inflammatory factors were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Apoptosis was detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Cell viability was determined by Cell Counting Kit-8 (CCK-8) test. Western blot was used to detect the expression levels of nuclear factor κB(NF-κB) p65, NF-κB inhibitor (IκBα), p-NF-κB p65 and p-IκBα.

Following LPS treatment, cytokine levels significantly increased compared to the control group.; moreover, cell proliferation decreased, apoptosis increased, and the expression level of p-NF-κB p65 was increased. Subsequently, the LPS-treated hEECs were exposed to notopterygium. Compared to the LPS group.

Treatment with LPS + notopterol resulted in a dose-dependent reduction in inflammatory cytokines, increased cell proliferation, and a significant reduction in apoptosis. Furthermore, the expression levels of p-NF-κB p65 and p-IκBα were downregulated.

These findings suggest that notopterol alleviates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway.

Diverse Phenotypic Expressions of ADA2 Deficiency: Two Case Studies

Anahita Razaghian — 2025-11-09

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessive disease with varying degrees of clinical phenotypes and disease severity. The phenotypic spectrum of the disorder has expanded from vasculitis with stroke to include pure red cell aplasia, bone marrow failure, autoimmune cytopenia, lymphoproliferation, and variable degrees of immunodeficiency.

Here, we describe two cases of ADA2 deficiency: one presented with an early-onset stroke that resembled an early-onset polyarteritis nodosa (PAN), and the other as an adult-onset vasculitis that progressed to severe neutropenia with recurrent infection and lymphoproliferation. Patient 1, a 10-year-old male, had a reported pathogenic ADA2 homozygote variant; c.139G˃C (p.Gly47Arg), and patient 2, a 34-year-old male, had a reported likely pathogenic homozygous ADA2 variant; c.578C>T (p.Pro193Lys).

Our second patient was the first DADA2 patient who showed that DADA2 is not a static disease and can progress from vasculitis to bone marrow failure in the course of the disease. Therefore, the previous recommendation introducing anti–TNF-α as a preferred treatment for vasculitis manifestations and hematopoietic stem cell transplantation as the preferred treatment for bone marrow failure can no longer apply. We should consider HSCT for DADA2 patients from the very beginning.

The Physician has to be aware of this monogenic disorder's varied presentation and multi-organ involvement. Early recognition and proper treatment are crucial for this potentially fatal disease.