Immunologic Research[JOURNAL]
Sun
200 papers
The impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis.
You J, Yang H
Immunol Res · 2025 Jul · PMID 40676385 · Publisher ↗
Neuroblastoma (NB) is a prevalent malignant tumor in children, primarily affecting the nervous system, with a high mortality rate, particularly in high-risk patients. This study aims to establish a neddylation-related pr...
Neuroblastoma (NB) is a prevalent malignant tumor in children, primarily affecting the nervous system, with a high mortality rate, particularly in high-risk patients. This study aims to establish a neddylation-related prognostic signature (NRPS) through the analysis of gene expression data from NB patients and to evaluate its clinical application potential. A comprehensive analysis was conducted using gene expression profiling, single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and single-sample gene set enrichment analysis (ssGSEA) to elucidate the role of neddylation and establish a NRPS for NB patients. Our analysis identified 171,992 cells categorized into 19 distinct clusters, revealing that Schwann and tumor cells exhibited significantly higher neddylation scores compared to other cell types. We constructed a NRPS that significantly impacts overall survival and event-free survival. Immune infiltration analysis demonstrated significantly higher levels of immune cells, particularly activated CD8 + T cells and natural killer cells, in the low-risk group, indicating a stronger anti-tumor immune response. Furthermore, gene set enrichment analysis (GSEA) revealed that the high-risk group was associated with cell division and DNA repair pathways, while the low-risk group showed enrichment in immune-related signaling pathways, suggesting immune activation may confer protective effects. Additionally, the immunotherapy analysis suggested that the low-risk score group exhibited better immunotherapy outcomes. This study underscores the clinical significance of NRPS in predicting survival and therapeutic outcomes in NB patients, highlighting their necessity and urgency in personalized treatment approaches.
Metabolic-associated enthesitis: a review on pathophysiology, clinical relevance, diagnostic challenges, and perspective on target treatments.
Lisco G, De Tullio A, Zupo R … +4 more , Prete M, Piazzolla G, Racanelli V, Triggiani V
Immunol Res · 2025 Jul · PMID 40646307 · Publisher ↗
Entheses are specialized tissues that connect ligaments and tendons to the bone surface and are frequently involved in seronegative spondyloarthritis. Enthesitis can also be detected in patients with metabolic disorders...
Entheses are specialized tissues that connect ligaments and tendons to the bone surface and are frequently involved in seronegative spondyloarthritis. Enthesitis can also be detected in patients with metabolic disorders (MD), regardless of baseline autoimmune rheumatic disease, posing real diagnostic challenges. The present review discusses the pathophysiology of enthesitis and metabolic-associated enthesitis, the clinical relevance of metabolic disorders on enthesitis-related outcomes, diagnostic challenges for adequate differential diagnosis, and possible therapeutic strategies to improve clinical outcomes. PubMed/MEDLINE and the Cochrane Library were searched for original articles, systematic reviews, and meta-analyses. References were screened according to a hierarchical analysis of studies by title, abstract, and full text, collected, presented, and discussed. Metabolic-associated enthesitis is attributable to mechanical stress/overload due to weight excess typically observed in metabolic disorders (MD), such as overweight/obese comorbid patients, metabolic syndrome (MS), and type 2 diabetes (T2D). Interleukin 1β, 6, 17, 18, and 23 and tumor necrosis factor-α play a crucial role in initiating and maintaining entheseal inflammation. Chronic hyperglycemia and insulin resistance lead to a vicious circle as they stimulate, upon activated, specialized T cells to produce these specific cytokines, thus maintaining entheseal inflammation chronically. MD is associated with more severe clinical presentation, worse response to pharmacological treatments, and poor entheseal outcomes also in patients with existing seronegative spondyloarthritis. Non-immune-mediated metabolic-associated enthesitis poses a real diagnostic challenge, possibly underestimating cases and potential misdiagnoses. From a therapeutic viewpoint, glucose control improvement and weight loss are associated with relevant amelioration of entheseal-related outcomes. Pharmacological and non-pharmacological interventions aiming to reduce body weight, improve glucose control and insulin sensitivity, and attenuate inflammation are desirable to achieve the therapeutic target. Glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter type 2 inhibitors, in add-on to non-steroidal anti-inflammatory drugs and immunomodulators when necessary, may have a therapeutic rationale in patients with metabolic-associated enthesitis. Awareness of metabolic-associated enthesitis is essential to improve the accuracy of differential diagnosis in patients with MD and prescribe appropriate therapeutic strategies. However, basic and clinical research is needed to understand the role of "antihyperglycemic" agents in better managing metabolic-associated enthesitis.
Dysautonomia: a common comorbidity of systemic disease.
Blitshteyn S
Immunol Res · 2025 Jul · PMID 40624434 · Full text
Referring to a broad spectrum of the autonomic symptoms, autonomic disorders, and general dysfunction of the autonomic nervous system, dysautonomia is one of the common and under-recognized comorbidities of a wide variet...
Referring to a broad spectrum of the autonomic symptoms, autonomic disorders, and general dysfunction of the autonomic nervous system, dysautonomia is one of the common and under-recognized comorbidities of a wide variety of systemic disease, including diabetes, autoimmune disorders, vitamin deficiencies, and hormonal dysregulation. The most common autonomic disorders encountered in clinical practice are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be undiagnosed or often mislabeled with psychiatric disorders. Typical clinical features of dysautonomia, such as orthostatic dizziness/lightheadedness, orthostatic intolerance, palpitations, exercise intolerance, cognitive dysfunction, and fatigue, should prompt a diagnostic investigation for dysautonomia, which includes an in-office 10-min stand test or a tilt table test in conjunction with other autonomic function tests if available. Treatment approach consists of non-pharmacologic and pharmacologic therapies with beta blockers, midodrine, ivabradine, pyridostigmine, fludrocortisone, stimulants, and other medications. In clinical setting, dysautonomia may present a diagnostic and therapeutic challenge in patients with various systemic disorders and may require a high index of suspicion on the part of the clinician. Importantly, diagnosing and treating dysautonomia is critical to providing comprehensive and personalized medical care to complex patients with chronic illness, who are typically highly symptomatic with multi-systemic complaints as a result of comorbid, and often undiagnosed, dysautonomia.
Immunological and clinical characteristics in a cohort of Colombian pediatric patients with 22q11.2 deletion.
Castano-Jaramillo LM, Sanguino-Lobo R, Maradei S … +1 more , Velez-Tirado N
Immunol Res · 2025 Jul · PMID 40615621 · Publisher ↗
22q11.2 deletion syndrome (22qDS) is a heterogeneous genetic disorder associated with a variety of clinical manifestations, including congenital heart disease, neuropsychiatric disorders, hypocalcemia, and immunological...
22q11.2 deletion syndrome (22qDS) is a heterogeneous genetic disorder associated with a variety of clinical manifestations, including congenital heart disease, neuropsychiatric disorders, hypocalcemia, and immunological deficiencies. This study aimed to characterize the clinical and immunological features of patients with 22qDS in a cohort from Colombia. We conducted a retrospective study over a 3-year period, including 40 patients with confirmed 22qDS. Demographic, clinical, and immunological data were collected from medical records. The cohort had a median age of 3 years, with a balanced sex distribution. Heart defects were present in 75% of patients, followed by ear and craniofacial abnormalities (50%) and language disorders (45%). Immunological work-up revealed low T cell subsets in 42% of patients, with a decrease in T cell lymphopenia observed with age. Humoral deficiencies were also common, with 20% of patients exhibiting selective IgM deficiency and 17% presenting with hypogammaglobulinemia. Recurrent infections were observed in 48% of patients, particularly pneumonia and otitis. Vaccine responses to protein-based antigens and polysaccharides were frequently impaired. The findings highlight the clinical and immunological heterogeneity of 22qDS in this Latin American cohort. Multidisciplinary care, early diagnosis, and immunological management are essential for improving outcomes in these patients.
Risk factors for infections in systemic lupus erythematosus: a meta-analysis.
Xuan Y, Wang J, Yuan Y … +4 more , Zhao X, Zuo F, Liu S, Wan L
Immunol Res · 2025 Jul · PMID 40613863 · Publisher ↗
Immune dysfunction in patients with systemic lupus erythematosus (SLE) increases susceptibility to infections, complicating their management. Identifying risk factors for infections is essential for improving clinical ou...
Immune dysfunction in patients with systemic lupus erythematosus (SLE) increases susceptibility to infections, complicating their management. Identifying risk factors for infections is essential for improving clinical outcomes. A meta-analysis was conducted to evaluate factors associated with infection risk in patients with SLE. Relevant studies were retrieved from PubMed, Web of Science, Embase, and Scopus databases from inception to November 2023. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using R software (version 4.3.1). Factors analyzed included age, gender, active disease stage, diabetes mellitus, kidney injury, hydroxychloroquine, high-dose glucocorticoids, immunosuppressive drugs, lymphopenia, anti-dsDNA, and complement 3 (C3). Twenty-one studies were included. The analysis identified several factors significantly associated with increased infection risk: age (OR = 1.02, 95% CI 1.01-1.04), being male (OR = 1.66, 95% CI 1.19-2.33), active disease stage (OR = 1.74, 95% CI 1.25-2.43), diabetes mellitus (OR = 1.64, 95% CI 0.92-2.93), kidney injury (OR = 1.78, 95% CI 1.37-2.30), high-dose glucocorticoids (OR = 2.40, 95% CI 1.88-3.80), immunosuppressive drugs (OR = 2.24, 95% CI 1.15-4.38), lymphopenia (OR = 3.59, 95% CI 2.42-5.33), and low C3 (OR = 2.38, 95% CI 1.13-5.03). Older age, male gender, active disease, diabetes, kidney injury, high-dose glucocorticoid use, immunosuppressants, lymphopenia, and decreased C3 levels may increase the risk of infections in SLE. These findings highlight the importance of individualized infection prevention strategies in high-risk patients.
Immunomodulatory activities of carbon quantum dots on the primary macrophages and whole splenocytes.
Ayaz F, Kavrak B, Bilakaya B … +3 more , Çamlik G, Özarslan FS, Değim İT
Immunol Res · 2025 Jun · PMID 40580345 · Publisher ↗
Quantum dots, because of some of their fascinating features, like continuous radiation emission, crossing the biological barrier, and potential for drug carrying, have emerged as versatile nanomaterials in enormous appli...
Quantum dots, because of some of their fascinating features, like continuous radiation emission, crossing the biological barrier, and potential for drug carrying, have emerged as versatile nanomaterials in enormous applications relating to drug development and health sciences. Among such quantum dots, carbon quantum dots have gained widespread attention due to their low toxicity, high biocompatibility, and excellent photostability. The present work investigates the immunomodulatory properties of CQDs with diverse chemical characteristics against primary macrophages and whole splenocytes. Since macrophages are important regulators of immune responses, their isolation and activation by toll-like receptor agonists were performed to evaluate the production of pro-inflammatory cytokines and intracellular signaling pathways. Our data indicate that different CQD formulations possess specific immunomodulatory activities, while some of them reveal adjuvant capabilities; others act anti-inflammatory. Importantly, the zinc-containing CQDs enhance pro-inflammatory responses, which may find applications as vaccine adjuvants. These findings highlight the therapeutic possibilities of CQDs in the treatment of inflammatory diseases and enhancement of vaccine efficacy.
The epidemiological trends of inflammatory bowel disease among women of reproductive age: a global analysis from 1990 to 2021.
Fan Z, Zhou H, Tian L … +8 more , Wu T, Zhang J, Lin J, Wang C, He J, Zhao L, Chen J, Liang J
Immunol Res · 2025 Jun · PMID 40576854 · Publisher ↗
This study aimed to evaluate the global burden of inflammatory bowel disease (IBD) among women of reproductive age (15-49 years) from 1990 to 2021, analyze its association with socio-demographic index (SDI), and identify...
This study aimed to evaluate the global burden of inflammatory bowel disease (IBD) among women of reproductive age (15-49 years) from 1990 to 2021, analyze its association with socio-demographic index (SDI), and identify age-period-cohort (APC) effects to inform region-specific public health strategies. Using data from the Global Burden of Disease (GBD) 2021 study, we assessed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (ASDR) across 204 countries. Statistical analyses included Pearson correlation to evaluate SDI associations, decomposition analysis to quantify burden drivers, and APC modeling to disentangle age, period, and cohort effects. In 2021, the global ASIR, ASPR, ASMR, and ASDR for IBD in women of reproductive age were 4.38, 45.90, 0.50, and 17.75 per 100,000, respectively. The health burden of IBD in women of reproductive age varies by region. Australasia has the highest ASIR and ASPR globally, while these metrics are lowest in Central Latin America. Western Europe exhibits the highest ASMR, whereas Oceania has the lowest. In terms of ASDR North America, with its higher income, bears the heaviest burden, while Oceania experiences the lightest. Furthermore, APC analysis revealed age-specific risks peaking at 45-49 years, and significant cohort effects in middle/low-SDI regions, where post-1977 birth cohorts showed elevated incidence. Period effects highlighted diverging trends: stable incidence in high-SDI regions vs. rising rates in mid-SDI regions due to urbanization and lifestyle shifts. The IBD burden among reproductive-aged women is rising disproportionately, shaped by SDI gradients and demographic transitions. High-SDI regions require strategies targeting aging populations and comorbidities, while low/middle-SDI regions need investments in early diagnosis and equitable care.
Immunomodulatory activity of 4-(Benzyloxy)phenol facilitates intracellular mycobacterial clearance through p53 mediated IL-35 signaling dependent JAK1/STAT3 pathway in human macrophages.
Naik L, Patel S, Das M … +8 more , Nayak DK, Dandsena PK, Quaderi MA, Kumar A, Mishra A, Singh R, Mishra A, Dhiman R
Immunol Res · 2025 Jun · PMID 40571857 · Publisher ↗
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), modulates host immune responses by regulating various cytokines. Precise regulation of these cytokines renders the host pathogen-fre...
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), modulates host immune responses by regulating various cytokines. Precise regulation of these cytokines renders the host pathogen-free, whereas their dysregulation increases the susceptibility to infection. Hence, induction of host protective cytokines using immunomodulators to promote M. tuberculosis clearance has a rewarding impact in the context of TB treatment. This study explored the immunomodulatory activity of 4-(Benzyloxy)phenol (4-BOP) in mycobacteria infected differentiated THP-1 cells through IL-35 (an anti-inflammatory cytokine) production. Initially, we observed an increased mRNA and protein level expression of IL-35 and its cognate receptor upon 4-BOP treatment in mycobacteria-infected dTHP-1 cells. IL-35 receptor activation further led to phosphorylation of JAK1/STAT3, culminating in increased phagosome-lysosome fusion through elevation of intracellular Ca level. Blocking IL-35 receptors using siRNA-mediated approach against IL-12Rβ2 and gp130 or the JAK1/STAT3 associated signaling with specific inhibitors like Baricitinib and Stattic promoted the intracellular mycobacterial survival by compromising Ca-phagosome-lysosome fusion pathway. Further, we identified a direct regulatory role of p53 (known to be activated by 4-BOP) on IL-35 production, and inhibition of p53 using PFT-α surprisingly abrogated the IL-35 mediated signaling axis. Collectively, our results demonstrated a host defensive role of 4-BOP-induced Il-35 signaling in mycobacteria-infected dTHP-1 cells through the JAK1/STAT3 mediated Ca-phagosome-lysosome fusion pathway. These results suggest that 4-BOP may serve as a potent HDT candidate for regulating inflammation and enhancing host defense in TB infection.
HBV infection upregulates GP73 expression to promote liver fibrosis by enhancing ER stress via the Smad2 pathway.
He Y, Cai L, Liu L … +4 more , Zhang Y, Si L, Cheng Q, Luo S
Immunol Res · 2025 Jun · PMID 40571844 · Publisher ↗
Endoplasmic reticulum (ER) stress induced by hepatitis B virus (HBV) infection is associated with the development of liver fibrosis. Golgi protein 73 (GP73) is increased during HBV infection. Nevertheless, whether GP73 d...
Endoplasmic reticulum (ER) stress induced by hepatitis B virus (HBV) infection is associated with the development of liver fibrosis. Golgi protein 73 (GP73) is increased during HBV infection. Nevertheless, whether GP73 during HBV infection mediates ER stress in liver fibrosis is still poorly understood. TGF-β1 was used to induce HepG2.2.15 cells to establish liver fibrosis cells model. GP73 expression was evaluated using qRT-PCR analysis and Western blot. HepG2.2.15 cells viability and proliferation were assessed via CCK-8 assay and EdU assay, respectively. The protein levels of α-SMA, fibronectin, collagen I and collagen III for liver fibrosis, GRP78, p-PERK, p-eIF2α, ATF4 and CHOP for ER stress, as well as p-Smad2 and Smad2 were evaluated by Western blot. TGF-β1 incubation obviously elevated GP73 expression, while GP73 knockdown reduced the GP73 levels in HBV-transfected HepG2215 cells. GP73 knockdown reversed the effects of TGF-β1 exposure on HepG2.2.15 cells viability and proliferation. The protein levels of liver fibrosis marker, ERS marker and p-Smad2 were remarkably increased following TGF-β1 stimulation, which were counteracted by GP73 silence or the application of 4-phenylbutyric acid (4-PBA). However, these results were opposite after tunicamycin (TM) treatment. In conclusion, knockdown of GP73 potentially impeded the advancement of liver fibrosis via mediating ERs through Smad2 signal pathway.
High expression of signal regulatory protein beta 2 marks a favourable prognostic AML subgroup and associates with increased sensitivity to phagocytosis.
Visser N, van der Meer NK, He Y … +3 more , Huls G, Schuringa JJ, Bremer E
Immunol Res · 2025 Jun · PMID 40560511 · Full text
Acute myeloid leukaemia is an aggressive hematologic malignancy that remains exceedingly difficult to treat despite recent advancements. High expression of CD47 on leukemic blasts interacts with the inhibitory receptor S...
Acute myeloid leukaemia is an aggressive hematologic malignancy that remains exceedingly difficult to treat despite recent advancements. High expression of CD47 on leukemic blasts interacts with the inhibitory receptor SIRP-alpha (SIRP-α) on innate immune cells, resulting in a strong "don't eat me" signal. Therefore, identifying AML patients who could benefit from immune-targeted therapies is crucial SIRP-β2 is predominantly expressed in myeloid cells and positively regulates innate anticancer immunity. Furthermore, endogenously expressed SIRP-β2 potentiates cancer cell trogocytosis by granulocytes. Here, we delineate the role of SIRP-β2 in AML. High expression of SIRP-β2 is independently associated with favorable overall survival (OS) and event free survival (EFS) independent of the ELN intermediate risk group. SIRP-β2 is more prevalent in the more committed FAB M4 and M5 subgroups. SIRP-β2 is also expressed on normal myeloid cells in patient samples, with higher expression on tumor-suppressive M1 macrophages than on adverse prognostic and tumor-supportive M2 macrophages. In line with this, co-culture of macrophages/neutrophils with ectopically expressed SIRP-β2 tumor cells results in an increased phagocytosis/trogocytosis treated with anti-CD47. These data indicate that AML patients with high SIRP-β2 AML expression could significantly benefit from innate immune-targeting therapies such as CD47 immune checkpoint inhibitor.
Statins and adhesion molecules: a review of a novel pleiotropic property of statins.
Sadeghi M, Dehnavi S, Shahbaz SK … +4 more , Koushki K, Butler AE, Jamialahmadi T, Sahebkar A
Immunol Res · 2025 Jun · PMID 40526251 · Publisher ↗
Statins were introduced as lipid-lowering agents that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase; they are commonly administered to reduce cholesterol levels for cardioprotective purposes. Further...
Statins were introduced as lipid-lowering agents that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase; they are commonly administered to reduce cholesterol levels for cardioprotective purposes. Further studies suggested that statins have cholesterol-reducing-independent properties and exert pleiotropic therapeutic properties, including antioxidant, anti-inflammatory, anti-fibrotic, neuroprotective, and other beneficial effects. Adhesion molecules, including selectins, integrins, cadherins, CD44, and the immunoglobulin superfamily (IgSF) members, are essential mediators for those biological functions. The current review discusses studies performed in in vitro and in vivo in physiological and pathological models focusing on adhesion molecules such as Lymphocyte function-associated antigen-1 (LFA-1), macrophage-1 antigen (Mac-1), P-selectin, E-selectin, very late activation antigens-4 (VLA-4), and nectins that are therapeutically targeted by different types of statins and that highlight the potential therapeutic utility of statins for diseases other than cardiovascular disease.
The relationship between self-reported immune fitness and salivary immune biomarker concentrations.
Išerić E, Hendriksen PA, Ulijn GA … +4 more , Zuurveld M, van de Loo AJ, Garssen J, Verster JC
Immunol Res · 2025 Jun · PMID 40500530 · Full text
Immune fitness refers to the body's ability to respond to health challenges by activating an appropriate immune response. Perceived immune fitness can be assessed using a single-item scale ranging from 0 (very poor) to 1...
Immune fitness refers to the body's ability to respond to health challenges by activating an appropriate immune response. Perceived immune fitness can be assessed using a single-item scale ranging from 0 (very poor) to 10 (excellent). The aim of the current study (n = 29 healthy volunteers) was to evaluate the relationship between perceived immune fitness and immune biomarker concentrations in saliva. Hourly assessments of immune fitness were made throughout the day (09:30 - 15:30), and saliva samples were collected accordingly. The concentrations of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) were determined using multiplex immunoassay. While immune fitness scores remained stable during the day, biomarker assessments showed some fluctuations. For IL-6, significant negative correlations were found between IL-6 concentration at 10:30 and immune fitness scores at 10:30 (r = -0.512), 11:30 (r = -0.383), and 12:30 (r = -0.443), and between the IL-6 concentration and immune fitness score at 15:30 (r = -0.704). For IL-8, significant correlations were found between IL-8 concentration at 10:30 and immune fitness scores at 10:30 (r = -0.480), 12:30 (r = -0.456), and 14:30 (r = -0.429). For TNF-α, significant positive correlations were found between TNF-α concentration at 13:30 and immune fitness scores at 13:30 (r = 0.517) and 14:30 (r = 0.477). No significant correlations were found between immune fitness and IL-1β. In conclusion, immune fitness scores remained stable throughout the day, and were significantly associated with salivary concentrations of IL-6, IL-8, and TNF-α at certain time points.
Staphylococcus aureus α-hemolysin induces DNA methylation changes in human Th1 cells.
Karwaciak I, Pastwińska J, Sałkowska A … +4 more , Karaś K, Sobalska-Kwapis M, Dastych J, Ratajewski M
Immunol Res · 2025 Jun · PMID 40498273 · Full text
α-Hemolysin is one of the most dangerous virulence factors produced by Staphylococcus aureus. Among the immune cells that respond to this pathogenic bacterium, Th1 lymphocytes play a critical role. In our study, we inves...
α-Hemolysin is one of the most dangerous virulence factors produced by Staphylococcus aureus. Among the immune cells that respond to this pathogenic bacterium, Th1 lymphocytes play a critical role. In our study, we investigated the impact of α-hemolysin on the methylation of the Th1 cell genome. Our findings revealed that α-hemolysin upregulates HELLS and DNMT3A expression while downregulating DNMT3L expression at the protein level. Whole-genome bisulfite sequencing analysis revealed significant alterations in DNA methylation, particularly in regions outside CpG sequences. These results suggest that bacterial proteins can act as potent epigenetic modulators in human cells, influencing their activity, plasticity, and phenotype.
FOXO1 contributes to cigarette smoke condensate-induced cellular senescence and fibrosis in lung fibroblasts through activating the TGF-β1/Smad2/3 signaling pathway.
Zheng M, Yuan G, Han J … +4 more , Li J, Jiang Y, Li Z, Yao Y
Immunol Res · 2025 Jun · PMID 40498253 · Publisher ↗
Cigarette smoking is the most dominant factor contributing to chronic obstructive pulmonary disease (COPD). Fibroblasts are sensitive to cellular injury induced by cigarette smoke condensate (CSC). This study was devoted...
Cigarette smoking is the most dominant factor contributing to chronic obstructive pulmonary disease (COPD). Fibroblasts are sensitive to cellular injury induced by cigarette smoke condensate (CSC). This study was devoted to discovering the potential target and exploring its regulatory mechanism in CSC-induced human fibroblasts. Network pharmacological analysis for differential genes in CSC-induced lung fibroblasts MRC5 was performed by a bioinformatics platform. COPD in vitro was induced by CSC in MRC5. The protein expression was analyzed by western blotting. Cellular senescence was tested by senescence-associated β-galactosidase assay and protein detection. Oxidative indexes were examined by corresponding kits. Inflammatory factors were detected using enzyme-linked immunosorbent assay. Markers associated with the TGF-β1/Smad2/3 pathway and fibrosis were also determined via western blotting. FOXO1 and TGF-β1 binding was analyzed by ChIP assay. An animal model was established to explore the effect of FOXO1 in vivo. Gene Ontology (GO) analysis of the differential genes in CSC-induced MRC5 cells indicated gene functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed the top 10 pathways. Forkhead box O 1 (FOXO1) was an upregulated gene in the cellular senescence pathway. Cell function assays suggested that FOXO1 knockdown restrained CSC-induced cellular senescence, oxidative stress, and inflammation in MRC5. FOXO1 downregulation inactivated the TGF-β1/Smad2/3 pathway and suppressed fibrosis markers in CSC-treated MRC5 cells. FOXO1 directly interacted with TGF-β1 promoter and facilitated cell senescence by upregulating TGF-β1. TGF-β1 abolished the suppression of TGF-β1/Smad2/3 pathway and fibrosis caused by FOXO1 knockdown. FOXO1 promoted COPD in mice by regulating the TGF-β1/Smad2/3 pathway. The obtained evidence affirmed that FOXO1 contributed to CSC-induced cellular senescence and fibrosis by promoting TGF-β1 transcription to mediate the TGF-β1/Smad2/3 pathway, indicating an important mechanism in the pathogenesis of COPD.
The mechanism of p38 MAPK, NF-κB, and IL-6 in T-2 toxin and/or selenium deficiency induced spleen injury.
Xiao X, Xiang R, Liu J … +6 more , Guo Z, Liu H, Lin X, Bao M, Angelo V, Han J
Immunol Res · 2025 Jun · PMID 40490651 · Publisher ↗
Both T-2 toxin and selenium (Se) cause immune impairment in the spleen, but the mechanism of their occurrence is not clear. In this experiment, the Se content of the spleen was tested by atomic fluorescence spectrometry...
Both T-2 toxin and selenium (Se) cause immune impairment in the spleen, but the mechanism of their occurrence is not clear. In this experiment, the Se content of the spleen was tested by atomic fluorescence spectrometry after a 12-week intervention in Sprague-Dawley (SD) rats, divided into normal, normal + T-2 toxin (10 ng/g), normal + T-2 toxin (100 ng/g), low Se, low Se + T-2 toxin (10 ng/g), and low Se + T-2 toxin (100 ng/g) groups. The pathological changes and fibrosis of spleen tissue were observed using hematoxylin-eosin (HE) staining and Masson staining, respectively. Mitogen-activated protein kinase p38 (p38 MAPK), phosphorylated protein-38 (P-p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) expression levels in spleen tissues were analyzed by Western blotting (WB) and immunohistochemistry (IHC) staining. This study found that both Se deficiency and T-2 toxin induced inflammatory injury and fibrotic changes in rat spleen, but low selenium and low selenium combined with T-2 toxin intervention showed more intense splenic injury. Se deficiency combined with T-2 toxin intervention aggravated spleen injury, and the mechanism of occurrence involved an increase in the inflammatory injury in the spleen by elevating the expression levels of p38 MAPK, NF-κB, and IL-6 in rat spleen.
Deucravacitinib as a monotherapy for concurrent management of psoriasis and chronic spontaneous urticaria.
Zhang X, Zhang C, Liang J … +3 more , Liu Y, Xu B, Li C
Immunol Res · 2025 Jun · PMID 40490621 · Publisher ↗
Patients with autoimmune diseases are susceptible to developing a second autoimmune disorder. Psoriasis, a common autoimmune disease, frequently occurs alongside other autoimmune conditions in some individuals. We report...
Patients with autoimmune diseases are susceptible to developing a second autoimmune disorder. Psoriasis, a common autoimmune disease, frequently occurs alongside other autoimmune conditions in some individuals. We report the case of a young female patient diagnosed with plaque psoriasis, initially treated with secukinumab, and achieved complete skin clearance at 12 weeks. However, she experienced a decline in the efficacy of secukinumab, with recurrence of symptoms and subsequent development of chronic spontaneous urticaria (CSU) and was switched to treatment with deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor. The use of deucravacitinib resulted in a favorable therapeutic outcome, effectively managing both psoriasis and CSU 12 weeks after treatment. This case highlights the potential of deucravacitinib as a novel monotherapy for patients with both psoriasis and CSU.
The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.
Sood A
Immunol Res · 2025 Jun · PMID 40488962 · Publisher ↗
The cGAS-STING pathway is a critical signaling mechanism in the innate immune system for sensing cytosolic DNA and subsequently facilitating antiviral responses. Cyclic GMP-AMP synthase (cGAS) recognizes both foreign and...
The cGAS-STING pathway is a critical signaling mechanism in the innate immune system for sensing cytosolic DNA and subsequently facilitating antiviral responses. Cyclic GMP-AMP synthase (cGAS) recognizes both foreign and self-DNA in the cytosol, resulting in the formation of 2'3'-cyclic GMP-AMP. STING is activated by the cyclic dinucleotide and drives the production of type I interferons as well as pro-inflammatory cytokines. Generating an inflammatory response through the cGAS-STING pathway is critical for antiviral defense, and this cascade also has been involved in the regulation of autophagy, cellular senescence, and other diseases. Defects in this pathway can result in autoimmunity, chronic inflammation, or increased cancer susceptibility. The molecular mechanisms underlying this pathway, its regulatory factors, and how it may contribute to diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and certain cancers were reviewed. This review further covers the therapeutic approaches to this system, such as agonists for cancer treatment and antagonists for autoimmune diseases.
STAT3 inhibition mitigates experimental autoimmune gastritis by restoring Th17/Treg immune balance.
Zhang A, Niu L, Ni Y … +4 more , Liu W, Gao X, Chang L, Cao P
Immunol Res · 2025 Jun · PMID 40471463 · Publisher ↗
This study investigates the role of STAT3 in autoimmune gastritis (AIG) pathogenesis and evaluates the therapeutic potential of STA-21, a STAT3 inhibitor. We utilized these models. (1) AIG model establishment using TxA23...
This study investigates the role of STAT3 in autoimmune gastritis (AIG) pathogenesis and evaluates the therapeutic potential of STA-21, a STAT3 inhibitor. We utilized these models. (1) AIG model establishment using TxA23 mice, (2) high-dose tamoxifen (HDT) treatment to induce gastric atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM), and (3) STA-21 administration to assess STAT3 inhibition. Mice were divided into TxA23 early-stage (2-4 months), advanced-stage (6-12 months), STAT3 knockout (TxA23 × STAT3⁻/⁻), and STA-21-treated (10 mg/kg/day for 1 month) groups. BALB/c mice were included for HDT experiments. HDT (80 mg/kg/day) and STA-21 (10 mg/kg/day) were administered by oral gavage for 1 month. Gastric tissues were analyzed to assess inflammation, immune cell populations, and cytokine expression. H&E staining evaluated histological changes, while immunohistochemistry assessed Ki67 (proliferation marker) and SPEM markers (TFF2, MUC6, CD44v9). Flow cytometry quantified CD4⁺IL-17⁺ (Th17) and CD4⁺FOXP3⁺ (Treg) cells, while qPCR and ELISA measured pro-inflammatory (IL-17, IL-21, IL-23R, RORγt) and anti-inflammatory markers (IL-10, FOXP3). STAT3 and p-STAT3 were significantly upregulated in TxA23 AIG mice, correlating with inflammation, atrophy, and mucus hyperplasia. STAT3⁻/⁻ mice exhibited reduced inflammation, preserved parietal cells, and suppressed epithelial hyperproliferation, alongside decreased SPEM markers (TFF2, MUC6, CD44v9). STA-21 treatment alleviated gastric atrophy, reduced inflammatory infiltration, suppressed Th17 differentiation, and enhanced Treg function, reversing the Th17/Treg imbalance. STAT3 inhibition alleviated autoimmune gastritis by restoring Th17/Treg balance, reducing inflammation, and potentially limiting early metaplastic changes, although long-term progression was not evaluated.
Role of the basophil activation test in the diagnosis and management of immediate drug reaction to injectable growth hormone preparation: a case report.
Barrale M, Romano S, Termini D … +2 more , Vinci D, Brusca I
Immunol Res · 2025 Jun · PMID 40465134 · Publisher ↗
Hypersensitivity reactions to synthetic hormones are rare but can represent serious complications. Allergic responses to synthetic human growth hormone (rhGH) pharmaceutical preparations are uncommon. Despite their rarit...
Hypersensitivity reactions to synthetic hormones are rare but can represent serious complications. Allergic responses to synthetic human growth hormone (rhGH) pharmaceutical preparations are uncommon. Despite their rarity, such reactions pose a significant clinical dilemma due to the associated risks and implications for ongoing treatment. Diagnosis is further complicated by the absence of standardized and commercially available in vitro tests, while in vivo testing carries the risk of systemic reactions, even at high dilutions. We report the case of a 6-year-old patient who experienced a severe reaction following rhGH administration. The diagnosis was investigated using the basophil activation test (BAT) prior to any in vivo testing. Given the potential risks of in vivo diagnostics, as previously reported in the literature, the BAT was employed to confirm the diagnosis and to identify a safe alternative rhGH formulation, which yielded negative results both in BAT and subsequent in vivo testing.
T-cell activation enhances anti-HER2-mediated antibody-dependent cellular cytotoxicity in gastric cancer.
Xue Z, Wang Z, Liu D … +6 more , Li B, Sun Z, Zhao J, Li H, Wang X, Sun Y
Immunol Res · 2025 Jun · PMID 40455140 · Publisher ↗
Anti-HER2 monoclonal antibody (mAb) is the standard first-line therapy for advanced HER2 gastric cancer. However, resistance to anti-HER2 therapy remains a significant clinical challenge. In this study, we identified a n...
Anti-HER2 monoclonal antibody (mAb) is the standard first-line therapy for advanced HER2 gastric cancer. However, resistance to anti-HER2 therapy remains a significant clinical challenge. In this study, we identified a novel resistance mechanism to anti-HER2 therapy in gastric cancer and proposed a strategy to enhance therapeutic efficacy by activating T cells. The association between intratumoral immune cells and clinical responses to anti-HER2 therapy in gastric cancer was investigated. Peripheral blood mononuclear cells (PBMCs) were co-cultured with HER2 gastric cancer cell lines or organoids to study NK cell responses mediated by anti-HER2 mAb. T cells were depleted or activated to assess their impact on antibody-dependent cellular cytotoxicity (ADCC), and the mechanism by which T cells influence ADCC was examined. The combinatorial effects of anti-HER2 mAb and HER2 × CD3 T cell-engaging bispecific antibody (bsAb) in gastric cancer were evaluated. A total of 35 gastric cancer patients receiving anti-HER2 mAb treatment were enrolled. A higher number of intratumoral T cells were associated with greater tumor regression and improved overall survival following anti-HER2 mAb therapy. Mechanistically, T cells, mainly CD4 T cells, influence NK cell functional and phenotypic changes via interleukin-2 (IL-2) production. Activating T cells by HER2 × CD3 T cell-engaging bsAb enhanced the anti-tumor effects of anti-HER2 mAb in gastric cancer. Our study identified the lack of T cell help as a novel resistance mechanism to anti-HER2 mAb in gastric cancer. Enhancing T cell help via the combination of HER2 × CD3 bsAb improved the therapeutic efficacy of anti-HER2 mAb in gastric cancer.
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