Central European Journal of Immunology最新文献

Introduction: The present study aimed to investigate the involvement of microfibril-associated protein 2 (MFAP2), a multifunctional secreted protein and constituent of extracellular matrix microfibrils, in the tumorigenicity of uterine corpus endometrial carcinoma (UCEC).

Material and methods: The mRNA expression levels of MFAP2A were detected in a total of 52 pairs of UCEC and adjacent non-tumorous tissues. Cell proliferation, migration and invasion, as well as cell apoptosis, were assessed using CCK8, Transwell and TUNEL assays, respectively. In addition, overall survival, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment and gene alterations were determined by bioinformatic analysis.

Results: The results showed that MFAP2 and transcription factor 7 like 1 (TCF7L1) were significantly upregulated in UCEC tissues compared with normal non-tumoral tissues. Also, a notable positive association between MFAP2 and TCF7L1 was observed in UCEC tissues. Furthermore, MFAP2 silencing notably attenuated the proliferation, migration, and invasion, and enhanced the apoptosis of UCEC cells. However, overexpression of MFAP2 abrogated the anti-tumor effect of TCF7L1 silencing on UCEC cell lines. Our study also revealed a negative correlation between MFAP2 and Immunoscore.

Conclusions: The present study suggested that MFAP2 could be involved in the carcinogenic progression of UCEC via the β-catenin/TCF7L1 axis. MFAP2 overexpression may contribute to immunosuppression in UCEC patients.

Introduction: Breast cancer (BC) remains a significant threat to women's health, necessitating the identification of new targets to inhibit its progression. Pyroptosis, a form of programmed cell death characterized by cellular swelling, distortion, and increased inflammatory factors, has emerged as a potential mechanism. High expression of exportin-T (XPOT) is linked to poor prognosis in BC patients, but its role in BC progression is not well understood.

Material and methods: We used the GEPIA database to analyze XPOT expression in BC and confirmed XPOT levels in BC tissues via immunohistochemistry. Western blotting was used to assess XPOT expression in various BC cell lines. We transfected small interfering RNAs (siRNAs) targeting XPOT and verified the transfection efficiency using Western blotting. The impact of si-XPOT on MCF-7 cell proliferation and apoptosis was measured using CCK-8 and TdT-mediated dUTP nick-end labeling assays. Scratch and Transwell assays were used to evaluate cell metastasis. Enzyme-linked immunosorbent assay was used to measure pyroptosis-associated inflammatory factors interleukin (IL)-1β and IL-18. Western blotting was used to detect pyroptosis-related proteins gasdermin D (GSDMD) and inflammasome components.

Results: XPOT expression was elevated in BC tissues, with higher levels in MCF-7 cells compared to other BC cells. Silencing XPOT reduced MCF-7 cell viability, migration, and invasion. Inhibition of XPOT increased pyroptosis-associated inflammatory factors, elevated N-terminal shear levels of GSDMD, and upregulated NLRP3, ASC, and cleaved-caspase1 expression. The pyroptosis inhibitor azalamellarin N reversed the effects induced by si-XPOT.

Conclusions: Silencing XPOT promotes pyroptosis in BC cells and inhibits BC progression, suggesting that targeting XPOT could offer new therapeutic avenues for BC treatment.

Although generalized edema is a rare adverse event after drugs or vaccinations, here we report a case of generalized edema with systemic inflammatory reaction clinically similar to incomplete systemic capillary leak syndrome (SCLS), potentially triggered by COVID-19 immunization. The patient presented with generalized subcutaneous edema, a drop in blood pressure, elevated inflammatory biomarkers, and hypoalbuminemia after receiving the vaccine, with no other apparent cause than vaccination. Comprehensive diagnostic evaluation revealed no specific underlying cause. She was treated with glucocorticosteroids successfully. This case underscores the importance of recognizing rare but severe adverse events associated with vaccinations. Given the widespread administration of COVID-19 vaccines, it is crucial to identify and understand such reactions to ensure timely diagnosis and management. Therefore, we review the existing cases of SCLS following COVID-19 vaccination. Our review highlights the need for heightened vigilance and further research into the mechanisms underlying vaccine-induced phenomena to improve patient outcomes and vaccine safety profiles.

Introduction: Lung adenocarcinoma (LUAD), the most prevalent lung cancer type, poses a great threat to public health, with its incidence and mortality rates remaining alarmingly high. While ankyrin repeat domain-containing protein 22 (ANKRD22) is linked to the development of multiple cancers, the molecular mechanisms of its impact on the malignant progression of LUAD are not yet fully understood. This study seeks to elucidate the biological role of ANKRD22 in LUAD.

Material and methods: ANKRD22 expression in LUAD tissues and cells was assessed using the TCGA-LUAD database and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The polarization of macrophages (derived from THP-1 cells) was examined through qRT-PCR, flow cytometry, and western blot to determine the influence of ANKRD22 on macrophage polarization. The effects of ANKRD22 knockdown on A549 cell proliferation and migration were measured using Cell Counting Kit-8 assay, colony formation, and Transwell assays. The impact of ANKRD22-induced macrophage M2 polarization on human umbilical vein endothelial cell (HUVEC) migration and angiogenesis was evaluated with Transwell and tube formation assays.

Results: The expression of ANKRD22 was elevated in LUAD tissue and cellular samples, and its overexpression promoted M2 polarization in macrophages. Blocking ANKRD22-mediated M2 polarization inhibited the migration and tube formation capacity of HUVEC cells.

Conclusions: Our findings showed that ANKRD22 mediates the malignant progression of LUAD by inducing M2 polarization of tumor-associated macrophages, thereby promoting angiogenesis.

This study aimed to investigate the mechanisms of innate immunosenescence in elderly patients with sepsis and to evaluate the potential application of innate immune modulation strategies in clinical management. Through a literature review, the characteristics of sepsis in the elderly, the aging mechanisms of the innate immune system, the impact of immunosenescence on susceptibility to sepsis, and clinical management strategies for sepsis in the elderly were analyzed. The incidence and mortality rates of sepsis in the elderly increase significantly with age, closely related to the severity of infection, the high prevalence of comorbidities, atypical symptoms, and a greater risk of multi-organ failure. Innate immunosenescence, including the decline in function of neutrophils, monocytes/macrophages, natural killer cells, and dendritic cells, is a key factor in the increased susceptibility to sepsis in the elderly. Immunomodulatory treatments, such as granulocyte colony-stimulating factor (G-CSF), interferon γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF), show potential in improving the prognosis of elderly patients with sepsis and reducing mortality rates. The management of sepsis in the elderly requires a comprehensive approach that takes into account age-related physiological and pathological changes, as well as early diagnosis and proactive intervention measures. Immunomodulatory strategies targeting the unique characteristics of immunosenescence in the elderly offer new avenues for improving survival rates and treatment outcomes in elderly patients with sepsis.

Introduction: T cell immuno-metabolic regulation plays a key role in the development of systemic lupus erythematosus (SLE). This study aimed to analyze the role of CD4⁺ T cell glucose metabolism in SLE development.

Material and methods: Clinical data and blood samples were collected from 20 untreated SLE patients and healthy controls (HCs) matched for age, sex, and body mass index. After being isolated by magnetic sorting and cultured with anti-CD3/CD28 for 72 h, CD4⁺ T cells were subjected to real-time metabolic analysis. CD4⁺ T cell proliferation and cytokines were measured with cell counting kit-8 and Luminex liquid chip assay, respectively.

Results: Compared to HCs, SLE-CD4⁺ T cells exhibited significantly higher glycolytic capacity and mitochondrial oxidative phosphorylation (OXPHOS) (both p < 0.001). Additionally, SLE-CD4⁺ T cells demonstrated increased proliferation rates and elevated cytokine levels in both plasma and culture supernatants (both p < 0.05). OXPHOS and glycolysis of SLE-CD4⁺ T cells were positively correlated with SLE disease activity index-2000 (SLEDAI-2K) and cytokines, and negatively correlated with SLE-CD4⁺ T cell numbers (all p < 0.05).

Conclusions: CD4⁺ T cells from SLE patients showed higher glucose metabolic activity than those from HCs, and the enhanced glucose metabolism of SLE-CD4⁺ T cells was strongly correlated with disease activity, suggesting that glucose metabolic reprogramming plays an essential role in the pathogenesis of SLE.

In the landscape of tumor immunotherapy, T cell-mediated immune responses have consistently captured the attention, while the contributions of B cells have been neglected. Nevertheless, growing evidence underscores the pivotal role of tumor-infiltrating B cells and plasma cells, collectively termed tumor-infiltrating B lymphocytes (TIL-B), in cancer treatment. These cells not only contribute significantly to therapeutic outcomes and prognostication in the realms of standard treatment and immune checkpoint inhibition but also open avenues for novel immunotherapeutic strategies. Interestingly, the heterogeneity within TIL-B populations, marked by diverse phenotypic subgroups, provides them with the capacity to exert both antitumor and protumor influences. Therefore, a comprehensive understanding of TIL-B interactions with tumors would be helpful for harnessing TIL-B as targets in tumor immunotherapy. Here, we survey the current state of TIL-B research with the aim of elucidating their role in tumor immunotherapy and offering insights for the development of TIL-B-based therapeutic approaches.

Introduction: Dermatomyositis (DM) is the most prevalent disease among myositis patients. The immune response is crucial in DM development. Bioinformatics research on immune-related genes in DM is limited. This study attempted to construct a diagnostic model and investigate immune characteristics of immune-related differentially expressed genes (DEGs), which could aid in DM diagnosis.

Material and methods: GSE46239 and GSE39454 datasets were from the GEO database, and batch effects were eliminated for use as the DM training set. DEG were identified and enrichment analysis was conducted between DM and normal samples. Intersection of DEGs and immune-related genes yielded immune-related DEGs, which were utilized to generate a PPI network. The diagnostic model was built by the LASSO method. The diagnostic model and effectiveness of model genes were evaluated through GSE143323. The correlation between immune cell infiltration in DM and diagnostic genes was analyzed. Finally, expression levels of HLA genes in DM and their correlation with diagnostic genes were examined.

Results: A total of 350 DEGs were identified. Seventy-one immune-related DEGs were screened. LASSO regression identified 5 immune-related DEGs (ACKR1, DHX58, IRF7, ISG15, and PSMB8) for constructing the DM diagnostic model. The model showed good effectiveness in training and validation sets (AUC of 0.99 and 0.958, respectively), and 5 immune-related DEGs also exhibited good effectiveness (AUC > 0.784). Diagnostic genes in DM were associated with M1 macrophages, M2 macrophages, resting dendritic cells, and certain HLA genes.

Conclusions: We constructed a DM diagnostic model using ACKR1, DHX58, IRF7, ISG15, and PSMB8, which were closely related to immune cells and HLA. This model could contribute to research in DM diagnosis.