Central European Journal of Immunology最新文献

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.

Introduction: The PD-1/PD-L1 immune checkpoint pathway plays a critical role in tumor immune escape and disease progression. This study investigated differences in tumor-infiltrating lymphocytes (TILs) and PD-L1 expression between primary breast cancers and matched metastatic lesions, and their relationships with clinical outcomes.

Material and methods: We retrospectively analyzed 54 female breast cancer patients who underwent radical mastectomy between May 2011 and December 2018 at the Second Affiliated Hospital of Nanchang University and later developed recurrent disease. Immunohistochemical (IHC) analysis was performed on matched primary and metastatic tumor samples to evaluate TILs and PD-L1 expression patterns. Associations between these immune parameters and clinical characteristics were assessed.

Results: IHC analysis of 50 paired primary and metastatic lesions revealed distinct PD-L1+ TIL expression patterns across different molecular subtypes of breast cancer. Patients with PD-L1+ tumors showed significantly shorter median disease-free survival (DFS) and overall survival (OS) compared to those with PD-L1- tumors. We observed significant differences in the immune microenvironment between primary and metastatic sites, with metastatic lesions showing consistently lower TIL density, PD-L1+ TIL density, and tumor PD-L1 expression compared to matched primary tumors.

Conclusions: Our findings demonstrate systematic differences in immune parameters between primary and metastatic breast cancer sites, with reduced immune infiltration in metastatic lesions. The data suggest that targeting the PD-1/PD-L1 pathway may be particularly beneficial in patients with PD-L1+ TIL-high primary tumors, potentially by reinvigorating anti-tumor immune responses.

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.

Introduction: Excessive mucus secretion in airway epithelial cells is a hallmark of various airway inflammatory diseases. Neutrophil elastase (NE) is a recognized inducer of mucus secretion, yet the precise mechanisms underlying this process remain inadequately understood. This study aims to investigate the roles of myristoylated alanine-rich C-kinase substrate (MARCKS), activated CDC42 kinase 1 (ACK1) and cortactin in airway mucin secretion induced by NE.

Material and methods: Human airway epithelial cells were treated with NE following specific siRNA- mediated knockdown of MARCKS, ACK1 and cortactin. Western blotting and immunofluorescence were used to observe the expression and localization of cortactin, MARCKS and ACK1. The interaction between cortactin and ACK1 was analyzed using co-immunoprecipitation, and MUC5AC protein expression was measured using ELISA.

Results: NE stimulation only increased the phosphorylation levels of MARCKS, ACK1, and cortactin in the cells. Silencing MARCKS inhibited the phosphorylation of ACK1, and silencing ACK1 inhibited the phosphorylation of cortactin. Co-immunoprecipitation showed that ACK1 could directly bind to cortactin. The inhibition of MARCKS and cortactin significantly decreased the production of MUC5AC.

Conclusions: NE induces the phosphorylation of MARCKS, which subsequently facilitates the phosphorylation of ACK1. This cascade enhances the phosphorylation of cortactin, ultimately leading to increased mucus secretion. The MARCKS/ACK1/cortactin pathway is a potential therapeutic target for excessive mucus secretion induced by NE.

Introduction: Allergic rhinitis (AR) is a common inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE). Astaxanthin (AST) has been demonstrated to attenuate airway inflammation in an asthmatic mouse model. Nonetheless, the precise effect of AST on AR symptoms and the associated mechanism remain unclear.

Material and methods: A mouse AR model was established by ovalbumin (OVA) sensitization and challenge, and AST was administered to AR mice. Human nasal epithelial cells (HNEpCs) were stimulated with recombinant human IL-13 to mimic the AR microenvironment in vitro. Hematoxylin-eosin staining was performed for mouse nasal mucosa histologic analysis. The CCK-8 assay was used to evaluate AST cytotoxicity to HNEpCs. ELISA was employed to determine levels of histamine, OVA-specific IgE, and inflammatory mediators. Oxidative stress-related markers were estimated using corresponding assay kits. Western blotting was implemented to estimate oxidative stress- and HMGB1/TLR4 signaling-related protein levels.

Results: AST administration alleviated nasal symptoms, including sneezing and nasal rubbing, in OVA-triggered AR mice. AST mitigated nasal mucosa pathological damage, reduced histamine, OVA-specific IgE, and inflammatory mediators in the serum, and alleviated oxidative stress in the nasal mucosa of AR mice. AST blocked HMGB1/TLR4/NF-κB signaling transduction in both the nasal mucosa of AR mice and IL-13-treated HNEpCs. AST or TAK-242 (a TLR4 inhibitor) ameliorated inflammatory response and oxidative stress in IL-13-stimulated HNEpCs.

Conclusions: AST treatment ameliorates AR by reducing inflammation and oxidative stress via the HMGB1/TLR4/NF-κB pathway.

Introduction: To explore the mechanism of action of azithromycin on lung oxidative injury and immune function in mice infected with Mycoplasma pneumoniae (MP) based on the nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway.

Material and methods: The lung index, dry/wet weight ratio, inflammatory factor levels in alveolar lavage fluid, serum contents of interferon-γ (IFN-γ) and immunoglobulin G (IgG), oxidative stress markers, peripheral blood levels of T-lymphocyte subsets, pathological changes, and Nrf2, HO-1, and NQO1 expression were assessed.

Results: Compared to the control group, the MP group exhibited elevated lung index, reduced lung dry/wet weight ratio, elevated tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 contents, reduced IL-10 levels, raised IFN-γ, IgG and peripheral blood CD8⁺ levels, reduced CD3⁺ and CD4⁺ levels, CD4⁺/CD8⁺ ratio, and superoxide dismutase (SOD) and glutathione (GSH) activity, elevated malondialdehyde (MDA) contents, destruction of lung tissue structure, elevated pathological scores, and diminished Nrf2, HO-1, and NQO1 levels. Compared with MP and MP + DMSO groups, MP + azithromycin (AZI) and MP + sulforaphane (SFN) groups displayed a reduced lung index, elevated lung dry/wet weight ratio, reduced TNF-α, IL-1β, and IL-6 contents, raised IL-10 content, decreased IFN-γ, IgG, and peripheral blood CD8⁺ levels, increased CD3⁺ and CD4⁺ levels and CD4⁺/CD8⁺ ratio, raised SOD and GSH activity, and diminished MDA content. HE staining demonstrated improved lung tissue structure, diminished pathological scores, and upregulated Nrf2, HO-1, and NQO1 levels after azithromycin and SFN intervention compared to the MP group (all p < 0.05).

Conclusions: Azithromycin ameliorates MP infection-induced lung injury and oxidative stress and strengthens immune function in mice, which may be achieved by activating the Nrf2/ARE signaling pathway.

This case report presents a 7-year-old boy with severe, early-onset cow's milk allergy (CMA) and poorly controlled, severe persistent asthma, highlighting the challenges of managing pediatric allergic multimorbidity. The patient experienced multiple anaphylactic reactions to cow's milk, significantly impacting his quality of life. Despite adherence to conventional asthma therapies, his asthma remained poorly controlled. Given the severity of his condition and the underlying immunoglobulin E (IgE)-mediated inflammation, treatment with omalizumab, an anti-IgE monoclonal antibody, was initiated. Following omalizumab initiation, significant improvements were observed in asthma control, including reduced symptoms, improved pulmonary function, and decreased airway inflammation. Additionally, although a formal oral food challenge after five months of treatment elicited an anaphylactic reaction, the threshold dose triggering the reaction was significantly higher than previous reactions, indicating an increase in tolerance to cow's milk proteins. This case underscores the potential of omalizumab in improving asthma control and increasing tolerance to cow's milk, with associated benefits to the patient, but also highlights the variability in response when targeting co-existing allergic conditions. Further research is needed to optimize treatment strategies for pediatric allergic multimorbidity.

Introduction: The immunopathogenesis of rheumatoid arthritis (RA) is greatly affected by macrophages. However, the precise mechanisms by which selenium-binding protein 1 (SELENBP1) regulates the interaction between macrophages and synovial fibroblasts remain incompletely understood.

Material and methods: We used macrophages (THP-1) that were activated with lipopolysaccharide (LPS) and interferon γ (IFN-γ), combined with gene knockdown techniques and molecular biology assays, to investigate the role of SELENBP1 in oxidative stress and nuclear factor erythroid 2-related factor 2 (NRF2) signaling activation. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assay were used to examine the regulatory effect of macrophage on proliferation and migration of synovial fibroblasts (MH7A).

Results: Bioinformatics analysis revealed significant upregulation of SELENBP1 in RA. LPS/IFN-γ treatment significantly increased SELENBP1 expression in THP-1 cells; promoted reactive oxygen species (ROS) production and oxidative stress, downregulation of NRF2 in the THP-1 cell nucleus, and upregulation of NRF2 in the cytoplasm; and increased proliferation and migration of MH7A cells. Knockdown of SELENBP1 reversed these effects of LPS/IFN-γ on the THP-1 and MH7A cells. In addition, ML385 (NRF2 inhibitor) attenuated the inhibitory effect of SELENBP1 knockdown on the ROS production and oxidative stress of THP-1 cells, as well as proliferation and migration of MH7A cells.

Conclusions: Inflammatory macrophages up-regulated SELENBP1, and knockdown of SELENBP1 inhibited inflammatory macrophage-induced ROS production and oxidative stress levels by activating NRF2 signaling, thereby inhibiting the proliferation and migration of synovial fibroblasts. Highly expressed SELENBP1 promoted the development of RA. These discoveries provide potential molecular targets and mechanistic insights for the development of new therapeutic strategies.