Immunologic Research最新文献

Osteoarthritis (OA) is the most common form of arthritis, and as the population ages, the incidence and prevalence of OA are projected to rise, particularly affecting women. This study investigates the association between female reproductive factors (age at menarche, menopause, gravidity, parity, and reproductive lifespan) and OA in women ≥ 50 years old using data from the United States National Health and Nutrition Examination Survey (NHANES). NHANES data from 1999 to 2018 of women ≥ 50 years old with complete arthritis questionnaires and other data of interest were reviewed. Reproductive factors were analyzed as continuous and ordinal variables. Covariates included age, race/ethnicity, body mass index (BMI), poverty income ratio, smoking status, and comorbidities such as hypertension, cardiovascular disease, and diabetes. A total of 10,133 women were included in the analysis. A later age at menarche was associated with a lower likelihood of OA (adjusted odds ratio [aOR] = 0.91, 95% confidence interval [CI]: 0.87-0.95, p < 0.001), and higher parity was associated with a lower likelihood of OA (aOR = 0.94, 95% CI: 0.91-0.97, p < 0.001). Stratified analysis showed that these associations were evident in specific subgroups, including women aged 60-69 years and those with obesity, but were not observed in other groups. Later age at menarche and higher parity are associated with a lower likelihood of OA in women. The cross-sectional nature of the study limits causal inferences; thus, further research is needed to explore potential causality.

Diabetic cardiomyopathy (DCM) is an irreversible chronic cardiovascular complication of diabetes with a high mortality rate. This study aimed to explore the role of methyltransferase-like 14 (METTL14)-mediated m6A modification in DCM. Here, DCM mouse models and high glucose (HG)-induced H9C2 cell models were employed. Cell phenotype was assessed using CCK-8 assay, lactate dehydrogenase (LDH) assay, Western blot, and flow cytometry. The underlying mechanism was investigated using quantitative real-time PCR (qPCR), methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assay. The results showed that METTL14 was upregulated in vitro and in vivo. Downregulation of METTL14 inhibited pyroptosis and myocardial damage. Mechanistically, METTL14 enhanced NLRP3 stability through m6A modification of NLRP3. Moreover, the m6A reader protein YTHDF1 (YTH N6-methyladenosine RNA-binding protein 1) mediated NLRP3 upregulation. This study revealed a novel mechanism by which METTL14-mediated m6A methylation regulates DCM progression, providing a potential therapeutic target for DCM.

Standardised diagnostic criteria for monogenic lupus are lacking owing to its rarity, diverse phenotypes, and significant heterogeneity in pathogenesis, phenotypic characteristics, disease course, and outcomes. Further, no studies have analysed the characteristics of multiple pathological mechanisms of monogenic lupus. Therefore, we retrospectively summarised the clinical characteristics, genotypes, and treatment of 36 patients with monogenic lupus with 16 different gene mutations admitted to the Department of Immunology at Beijing Children's Hospital between June 2021 and July 2024. Children with classic lupus were randomly allocated to the control group. A univariate analysis was conducted on different pathogenic pathways to identify relevant significant risk factors. The least absolute shrinkage and selection operator and logistic regression were applied to construct multiple models. The discrimination and calibration abilities of these models were then evaluated, and the optimal diagnostic model for each pathway was proposed. We found that increased vigilance for monogenic lupus is necessary for male children with an onset age of < 8.46 years and a family history. Type-I-interferon disorders should be considered in patients with growth retardation, interstitial lung disease, intracranial calcifications, characteristic rashes, splenomegaly, and elevated liver enzymes. Monogenic lupus involving immune tolerance pathways should be considered in patients with repeated infections, lymphoproliferation, or elevated double-negative T-lymphocyte proportion. Monogenic lupus caused by another pathway should be considered in patients with abdominal symptoms, oral ulcers, and elevated C-reactive protein levels. Overall, our study proposes distinct diagnostic models based on various pathogenic pathways, aiding in early identification and diagnosis of monogenic lupus in children.

Clusters of Differentiation (CD) molecules are cell surface molecules that exhibit dynamic expression on immune cells. This plasticity characteristic of CD molecules is the basis for the high abundance and diversity of immune cell phenotypes. However, phenotypic associations of immune cells due to co-expression and mutual exclusion expression lead to some extent to a narrowing of the size of the immunophenotype repertoire. Therefore, a systematic exploration of the expression correlation including co-expression and mutual exclusion expression between CD molecules can help to reveal the co-phenotype and lost phenotypes during immunophenotyping analysis. In this study, using bioinformatics methods, we first confirmed that the conventional widely used Pearson and Spearman correlations are only suitable for co-expression but not for mutual exclusion expression analysis. Using bulk and single-cell RNA sequencing data, we systematically investigated the expression correlation and anti-correlation or mutual exclusion of 386 protein-encoding CD molecules in human CD4⁺ T cells, CD8⁺ T cells, B cells, NK cells, and monocytes. Highly correlated co-expression networks were identified in these cell types. Using flow cytometry, three CD molecules including CD58, CD63, and CD147 were experimentally validated to be significantly co-expressed in T cells. In particular, CD58 and CD147 showed a high correlation in either CD4⁺ or CD8⁺ T cells. Co-expression was also observed in T cells from patients with primary Sjögren's syndrome (pSS) and was found to be positively correlated with the increased cytotoxic potential of T cells. In addition, the combination of CD58 and CD147 provided a more precise definition of the T-cell phenotype, which would be beneficial for improving the diagnostic efficiency of pSS.

It has been reported that anlotinib exhibits antitumor efficacy in various cancers. However, the potential mechanisms by which anlotinib affects the immunosuppressive characteristics observed in tumor angiogenesis have not been fully elucidated. Therefore, we aimed to determine the potential of anlotinib in improving the effectiveness of PD-1/PD-L1 blockade therapy in lung cancer. An LLC mouse model was established by xenograft tumor model to evaluate the synergistic effects of anlotinib and anti-PD-1. Furthermore, changes in tumor vascular structure and T-cell infiltration were assessed using immunohistochemistry and flow cytometry. Clinical information from 198 lung cancer patients was collected to further analyze the relationship between Ki67 expression and patient survival as well as the synergistic effects. The study demonstrated that anlotinib successfully inhibited LLC cell growth. Additionally, anlotinib reduced related protein expressions in JAK2/STAT3 pathway. Mice in the anlotinib group exhibited lower expression levels of PD-L1 and VEGF-A and decreased intratumoral microvascular density. Moreover, PD-1/PD-L1 blockade combined with anlotinib promoted CD4 + T-cell infiltration into tumors, ultimately enhancing antitumor activity. Clinically, lung cancer patients treated with anlotinib and anti-PD-1 showed reduced Ki67 expression and improved survival rates. In conclusion, anlotinib improves tumor vascular structure and CD4 + T-cell infiltration by downregulating JAK2/STAT3 signaling, thereby enhancing the efficacy of PD-1 blockade in lung cancer.

Common Variable Immunodeficiency (CVID) is the most frequently encountered symptomatic primary immunodeficiency in clinical practice, presenting with heterogeneous clinical and genetic features. While traditionally considered polygenic, recent advances in genomic technologies have revealed monogenic causes in a significant subset of patients. This study aimed to investigate the genetic background of adult patients diagnosed with CVID or CVID-like phenotypes, using clinical exome sequencing (CES), focusing on atypical and syndromic presentations. Thirty adult patients fulfilling the ESID/PAGID criteria for CVID underwent CES. Genetic analysis targeted 451 immune-related genes, with variants interpreted according to ACMG guidelines. Pathogenicity was confirmed with Sanger sequencing. We detected potentially disease-related variants (TNFRSF13B, BTK, RAG1, SAMD9, NFKB2, PRKDC, CFTR, FCN3, IFIH1, ITGA3, and TNFRSF1A) in 12 of the 30 patients (40%). TNFRSF13B was the most frequently mutated gene among these patients. Deep phenotyping analyses revealed atypical findings included a hemizygous BTK variant mimicking CVID, a homozygous RAG1 variant consistent with leaky SCID, and a heterozygous SAMD9 variant not presenting with MIRAGE phenotype, and a homozygous ITGA3 insertion region variant that suggested a mild form of ILNED syndrome. Variants in CFTR, FCN3, and TNFRSF1A further expand the phenotypic spectrum, highlighting overlap between immunodeficiency and immune dysregulation syndromes in adulthood. A substantial proportion of adult patients with CVID-like phenotypes harbor variants in genes beyond the classical CVID-associated loci. Our findings support the utility of broad genetic screening in adult-onset antibody deficiency, particularly when non-infectious complications are present. Molecular diagnosis facilitates accurate classification, guides personalized treatment, and aids in genetic counseling.

This review explores the complex interplay between viral infections and psoriasis. It emphasizes how viruses like HIV, hepatitis, herpes, human papillomavirus, and SARS-CoV-2 can provoke and worsen psoriatic inflammation by disturbing immune balance. A key focus of the discussion is the IL-23/Th-17 pathway, which drives the production of proinflammatory cytokines that promote keratinocyte overgrowth and perpetuate chronic skin inflammation. Our article further investigates how disrupted intracellular pathways-such as those involving PI3K, Wnt signaling, and caveolin-affect the severity of the disease. This review supports the idea that viral infections can not only trigger psoriatic lesions but may also increase the risk of additional viral reactivation, thereby complicating the clinical picture of psoriasis. This thorough evaluation highlights the necessity for focused research to create innovative therapeutic strategies aimed at these viral triggers.

Sepsis, a life-threatening systemic infection, has long been recognized for its immediate risks, but its long-term consequences on health are increasingly evident, particularly in predisposing survivors to chronic cardiometabolic disorders (CMDs) such as atherosclerosis, insulin resistance, and dyslipidemia. Central to this process is trained immunity, where innate immune cells like monocytes, macrophages, and neutrophils undergo long-lasting epigenetic reprogramming after sepsis. This reprogramming, sustained by molecular pathways such as NF-κB, mTOR, and altered lipid metabolism, drives chronic inflammation, oxidative stress, and metabolic dysfunction, contributing to long-term cardiovascular diseases (CVDs) and metabolic disorders post-sepsis. This review explores the key mechanisms through which trained immunity bridges sepsis and CMDs, particularly focusing on epigenetic modifications such as histone acetylation, DNA methylation, and mitochondrial alterations. We discuss how trained immunity enhances immune cell activation, leading to persistent low-grade inflammation, lipid dysregulation, and impaired insulin sensitivity, all of which predispose sepsis survivors to CVDs. Additionally, we highlight potential therapeutic approaches targeting trained immunity, including statins, which reduce inflammation and immune reprogramming; metformin, which restores metabolic balance by activating AMPK and reducing oxidative stress; dimethyl fumarate (DMF), a potent Nrf2 activator that counteracts inflammation; and probiotics, which help restore gut microbiota balance and limit endotoxin-driven inflammation. These therapies offer promising strategies to mitigate long-term metabolic dysfunction and reduce the incidence of CMDs following sepsis. Understanding these mechanisms and developing targeted interventions may ultimately help prevent chronic cardiovascular and metabolic diseases in sepsis survivors and improve long-term outcomes.

In this paper, the study focuses on Type 1 Diabetes Mellitus (T1D), a chronic condition that affects the insulin-producing cells of the pancreas, requiring individuals to depend on external insulin for survival. We introduce a novel method for analyzing protein sequences by treating them as rigid bodies with mass and moment of inertia to assess sequence similarity. This method transforms the protein sequences into vectors using the moment of inertia tensor, with similarity calculated using Euclidean distance. Using this technique, we identified 24 genes linked to T1D, showing significant similarities to known T1D-related genes and highlighting their potential importance in the disease. Further, we conduct functional enrichment analysis for better understanding, which is very helpful for investigating their roles in various biological processes and molecular functions. The Gene Ontology (GO)analysis is crucial for prioritizing the identified genes and providing insights into their contributions to T1D pathophysiology. To combine the concepts from physics with computational biology, our research not only increases the understanding of T1D disease but also introduces an innovative approach for gene discovery and functional analysis in autoimmune diseases.

Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A mouse model of AIH was established by injecting ConA (i.v.), and PIC was administered as an intervention. The protective effect of PIC was evaluated by the liver function, liver pathology, and serum levels of inflammatory factors. Subsequently, network pharmacology was used to predict the pathways and targets of PIC in the treatment of AIH, and the predicted results were validated using flow cytometry, molecular docking, surface plasmon resonance (SPR) and so on. Finally, the immunosuppressive effect of PIC was further validated in a mouse heart transplantation model. PIC can improve liver function decline and reduce pathological liver damage, as well as inhibit the increase of serum inflammatory factor levels in mice with AIH induced by ConA. The protective effect is achieved by suppressing the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts and inhibit acute rejection reactions. These results indicated that PIC can significantly improve ConA-induced AIH in mice by inhibiting the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts in mice and inhibit acute rejection responses. The above results indicated that PIC may serve as a promising immunosuppressant and be effective for AIH.