Journal of Immunology Research最新文献

Introduction: NSAID-exacerbated respiratory disease (N-ERD) is a bronchial asthma phenotype characterized by the coexistence of NSAID hypersensitivity, lower airway symptoms, and severe chronic sinusitis with nasal polyps. This study examined the cytokine profiles in the upper airways of patients with N-ERD compared to those of patients with NSAID-tolerant asthma, allergic rhinitis (AR), and healthy controls.

Methods: 89 patients were included in the N-ERD, AR, asthma, and control groups. The minimally invasive nasosorption technique was used to collect nasal mucosal lining fluid. Inflammatory mediators were quantified using a Bio-Plex Multiplex System.

Results: IL-6 levels in nasal samples (NSs) were higher in all patient groups than in the controls. No significant differences were observed in the nasal levels of all analyzed cytokines between patients with N-ERD and those with asthma or AR alone. Cluster analysis identified two distinct inflammatory phenotypes within the N-ERD group based on nasal cytokine profiles, although these did not correlate with clinical features. A logistic regression model showed that only serum TNF-α levels and the severity of nasal obstruction significantly differentiated patients with N-ERD from the other groups.

Conclusion: The results demonstrate that while patients with N-ERD exhibit heterogeneity in upper airway inflammatory profiles, this does not necessarily translate into differences in clinical presentation.

Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has significant potential in treating various cancers; however, its effectiveness is often compromised by the tendency of TILs to become exhausted and dysfunctional. Revitalizing these essential immune cells is crucial for amplifying their antitumor efficacy. Our study investigates the influence of spermidine on the metabolic pathways of TILs, focusing on its critical contribution to T cell vitality. We assessed the impact of spermidine on glucose absorption, mitochondrial functionality, and energy production in TILs. The application of spermidine resulted in a pronounced improvement in mitochondrial functionality and energy production, indicated by a surge in mitochondrial numbers and enhanced activity of the tricarboxylic acid (TCA) cycle. Importantly, the suppression of mitochondrial metabolism negated the beneficial effects of spermidine on mitigating exhaustion and enhancing cellular activity, highlighting the essential role of mitochondrial metabolism in the action of spermidine. Our research suggests that modulation of metabolism by spermidine could be a potential strategy to strengthen the antitumor capabilities of TIL-based treatments, offering a promising method to better manage solid tumors.

Diet-induced obesity is a growing global health concern linked to various immunological alterations. Dendritic cells (DCs) are major regulators of the balance between pro-inflammatory and tolerogenic immune responses. Conventional Type 1 DCs (cDC1) contribute to oral tolerance by affecting the generation of food specific regulatory T cells (Tregs). Nevertheless, whether obesity affects cDC1/Treg pathways and the generation of food tolerance remains poorly understood. Here, we investigated the spatio-temporal impact of a high-fat, high-sugar diet (HFHSD) on the enteric immune system. Enteric immune composition was primarily altered by diet and intestinal region, independently of the duration of the dietary regimen. Notably, the lamina propria of animals fed with high-caloric diet was enriched in cDC1 overtime. While diet did neither reprogramme cDC1 gut-homing markers, nor costimulatory molecules nor cytokines, it increased intestinal cDC1 levels, which correlated with increased Tregs during oral tolerance protocols. Our findings contribute to a better understanding of high-caloric diet and food intolerances, while revealing a remarkable plasticity of the intestinal immune system in response to diet.

Liver disease impacts millions of Americans every year, which is compounded by the comorbidities and consequences that patients are susceptible to developing. Hepatic encephalopathy (HE) is a severe consequence of liver failure resulting in a range of cognitive deficits that heavily impact quality of life. Approximately 40% of acute liver failure (ALF) patients and 50% of chronic liver disease patients will be diagnosed with HE, and the associated prognosis is 44% and 42%, respectively. Though understanding of some of the neurologic impacts of liver impairment exists, the pathology of HE is not yet fully elucidated. Many in the field have come to appreciate the role of neuroinflammation in its pathogenesis. In this review, we have summarized recent studies investigating aspects of neuroinflammation such as microgliosis, astrogliosis, proinflammatory cytokine and chemokine production, and the involvement of the choroid plexus and meninges in HE.

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) is caused by a pathogenic variant in the magnesium transporter 1 (MAGT1) gene. The defect leads to impaired N-glycosylation which affects various immune processes. In this study, we described the disease course, clinical features and laboratory parameters observed in six patients from three families diagnosed with XMEN syndrome. They exhibit heterogeneous clinical manifestation while displaying typical laboratory signs of the disease, including decreased surface expression of NKG2D and CD28 on CD8⁺ T-cells and NK cells, as well as defects in the N-glycosylation of transferrin. We identified two novel variants in the cohort: a frameshift variant c.444dup in exon 3, and a splicing variant c.998-20_1008del. Notably, a patient with the c.444dup variant presented with severe autoimmune cytopenia as an isolated manifestation of the disease, while his younger brother, carrying the same variant, exhibited predominantly mild skin infections. These findings illustrate varying degrees of severity in penetrance and highlight that some patients may exhibit only partial symptoms. Furthermore, our study confirmed defects in perforin expression in XMEN syndrome. We observed a significant reduction in perforin expression within CD8⁺ T-cells and NK cells which may lead to increased susceptibility to recurrent infections and autoimmune complications frequently observed in XMEN patients.

Introduction: More than 6 million deaths from the novel coronavirus, the Coronavirus disease 2019 (COVID-19) infection, have prompted the development of several prophylactic vaccines of COVID-19. This systematic review summarizes the ocular complications of various COVID-19 vaccinations, diseases diagnosed, treatment, and risk factors.

Methods: The search was done in PubMed, Web of Science (WOS), and Google Scholar databases. Manifestations were classified depending on the type of vaccines and the interval between vaccination and the onset of symptoms. Other data such as patients' age, gender, underlying diseases, and follow-up data were also extracted.

Results: Initially, 10,242 articles were identified and 76 articles were eligible that among them 107 cases were reported. Ocular complications were diagnosed more often in Pfizer-BioNTech COVID-19 vaccine and Oxford-AstraZeneca COVID-19 vaccine (AstraZeneca) recipients than in others.

Conclusion: This systematic review highlights a wide range of ocular complications reported after COVID-19 vaccination, the most common of which is uveitis. While most cases were mild and self-limiting, some involved reactivation of preexisting inflammatory diseases. These findings emphasize the importance of postvaccination ocular surveillance. This is particularly important in individuals with a history of ocular inflammation and suggests a potential immunological mechanism that requires further investigation.

Background: The urokinase plasminogen activator receptor (uPAR) plays a crucial role in cancer development and progression, making it an attractive target for immunotherapeutic strategies. This study aimed to develop a multiepitope vaccine targeting uPAR by incorporating T cell epitopes and a toll-like receptor 4 (TLR4) agonist as an adjuvant.

Methods: Immunoinformatics approaches were employed to predict and select immunogenic epitopes from the uPAR protein sequence. The selected epitopes were assembled into a multiepitope vaccine construct, including a TLR4 agonist derived from Mycobacterium tuberculosis as an adjuvant. The vaccine candidate underwent comprehensive in silico analyses, including antigenicity, allergenicity, physicochemical properties, and structural modeling. Molecular docking and molecular dynamics (MD) simulations were performed to evaluate the vaccine's interaction with the TLR4 receptor and assess its structural stability. Also, vector design was performed using the SnapGene software, while immune response simulations were conducted with the C-ImmSim server.

Results: The multiepitope vaccine construct comprised five cytotoxic T lymphocyte (CTL) epitopes, five helper T lymphocyte (HTL) epitopes, and the TLR4 agonist adjuvant. The vaccine was predicted to be nonallergenic, antigenic, and soluble, with favorable physicochemical properties. Molecular docking analysis revealed a strong binding affinity between the vaccine and TLR4, with a docking score of -334.37kcal/mol. MD simulations demonstrated the structural stability and rigidity of the vaccine-TLR4 complex. The computational immune simulation predicted a strong vaccine response with lasting antibody production, robust cellular immunity, and immunological memory formation.

Conclusion: The proposed multiepitope vaccine construct, consisting of carefully selected uPAR epitopes and a potent adjuvant, exhibits promising characteristics for inducing a robust immune response against cancer cells expressing uPAR. The favorable in silico results warrant further experimental validation and preclinical studies to assess the vaccine's efficacy and potential as a cancer immunotherapeutic agent.

Cutaneous lupus erythematosus (CLE), a common clinical manifestation of lupus erythematosus (LE), significantly compromises patients' quality of life and social functioning due to its relatively high prevalence. While the exact pathogenesis of CLE remains incompletely understood, accumulating evidence highlights the pivotal role of interferon (IFN) as a central mediator in disease initiation and progression. Stromal cells and infiltrating immune cells within CLE lesions demonstrate elevated expression of IFN-stimulated genes (ISGs), establishing a characteristic IFN signature. IFN orchestrates multiple pathological processes, including chemokine-mediated immune cell recruitment, cutaneous inflammation cascade, and tissue fibrosis. This review systematically examines the IFN-CLE axis through an integrated analysis of in vitro and in vivo experimental data. Emerging clinical trials reveal therapeutic promise in strategies targeting plasmacytoid dendritic cells (pDCs), neutralizing IFN signaling, or blocking downstream pathways. Given the current limitations in CLE management, IFN-focused strategies may offer innovative solutions to address unmet clinical needs through precision immunomodulation.

Atherosclerosis (AS) is a disease characterized by the presence of lesions in the arterial intima throughout the circulatory system. Lipid metabolism disorders form the pathological basis of AS. Immune injury resulting from lipid deposition, which is regulated by various cytokines, significantly contributes to disease progression. Follicular helper T (Tfh) cells are essential in the humoral immune response. The abnormal expression of surface molecules and cytokines by Tfh cells may contribute to the onset and progression of AS. Additionally, an increase in the Tfh cell population contributes to the progression of AS and coronary artery disease (CAD). Therefore, the targeting of Tfh cells and their associated functional molecules could serve as a promising therapeutic strategy against AS. This review summarizes current insights into the role of Tfh cells in AS and highlights their potential as therapeutic targets.

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD). Leonurine is an active component in Leonurus japonicus, involved in several processes such as inflammation, oxidation, and other processes. This study found that symptoms of colitis induced by 3% dextran sulfate sodium (DSS) solution in C57BL/6 mice were significantly alleviated after administration of leonurine, in terms of reduced body weight, shortened colon length, disease activity index (DAI), and colonic pathological damage. The expression of the tight junction (TJ) protein claudin-1 and occludin markedly increased, the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) significantly decreased. Findings from transmission electron microscopy (TEM) and intestinal permeability assessment experiments indicated that leonurine ameliorates the intestinal barrier. Leonurine regulated the pancreatic secretion pathway, significantly reduced the expression levels of Cela2a and Cela3b, and clearly decreased the abundance of Rikenellaceae_RC9_gut_group, UBA1819, Enterococcus, and Oscillibacter. We proposed that leonurine may improve DSS-induced colitis by regulating the pancreatic secretion pathway, modulating the gut microbiota, and improving intestinal barrier, potentially becoming a candidate for the treatment of UC.