Central European Journal of Immunology最新文献

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.

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.

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.

Cardiotoxicity caused by immune checkpoint inhibitors is one of the most severe and potentially fatal side effects. Hence it is crucial from a therapeutic standpoint to understand the underlying processes and devise countermeasures. This study sought to determine whether the SOCS3/JAK/STAT3 signaling pathway, which controls macrophage polarization, contributes to the cardiotoxicity caused by PD-1/PD-L1 inhibitors. The PD-1/PD-L1 inhibitor BMS-1 (10 mg/kg) was used to create a mouse model of immune checkpoint inhibitor-related cardiotoxicity, and hematoxylin and Masson's trichome tests were used to measure cardiomyocyte apoptosis and cardiotoxicity. The production of M1 factors (tumor necrosis factor α [TNF-α] and interleukin [IL]-1 b), as well as the blood levels of myocardial enzymes (creatine kinase, aspartate transaminase, creatine kinase-MB, and lactate dehydrogenase), were evaluated by ELISA. Echocardiography was used to assess the heart's health. The processes were investigated using flow cytometric analysis, real-time PCR, Western blot, and chromatin immunoprecipitation. We found that the PD-1/PD-L1 inhibitor BMS-1 dramatically reduced tumor weight while considerably impairing cardiac function in melanoma-induced tumor-bearing mice. At the gene and protein levels, it was found that levels of SOCS3, JAK, STAT3, and the inflammatory mediators IL-6 and TNF-α had all significantly decreased. Immune checkpoint inhibitor-induced cardiotoxicity may be linked to major changes in the SOCS3/JAK/STAT3 signaling pathway, as indicated by the knockdown of SOCS3, JAK, and STAT3. Finally, immune checkpoint inhibitor intervention demonstrated a large elevation of CD86+ and MHCII+ as well as a considerable increase in macrophages. These data suggest that the SOCS3/JAK/STAT3 signaling pathway, which controls macrophage polarization, may be linked to cardiotoxicity caused by PD-1/PD-L1 inhibitor therapy.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease whose treatment is still a challenge. The latest registration of anifrolumab for the treatment of moderate-to-severe SLE raises hopes because of its novel anti-interferon mechanism of action. Anifrolumab, a human monoclonal antibody, selectively binds the interferon α (INF-α) receptor, inhibiting systemic inflammation moderated by interferon pathways. The article presents the first case of an 18-year-old man with severe, relapsing and repeatedly hospitalized SLE, successfully treated with anifrolumab. During a subsequent exacerbation with multi-organ involvement, which could not be controlled despite pulses and high doses of glucocorticoids (GCSs), treatment with anifrolumab was initiated. Clinical improvement was achieved 4 weeks after the first dose. The patient's dose of systemic GCSs was gradually reduced until complete withdrawal. No serious side effects were observed throughout the follow-up period, and the criteria for complete remission were achieved by the patient at month 3 of therapy. After 12 months, therapy was discontinued due to a payer decision. Nevertheless, the patient remains in follow-up 14 months after the completion of therapy on stable treatment with hydroxychloroquine and azathioprine. He is still not taking prednisone. This is the first case in Poland to show the fate of a "real life patient" after completion of anifrolumab therapy, an effective clinical remission of many months without the use of oral GCSs.

The meta-analysis by Wang et al. aimed to assess the long-term effects of mesenchymal stem cells on complex perianal fistula. The authors concluded that mesenchymal stem cell therapy has a long-term effect on the clinical response of complex perianal fistula and should be widely promoted not only in adults but also in infants and adolescents; however, more research on this topic is needed. We appreciate the authors' hard work, and we also agree with this argument. However, we have several concerns about the study. We think it is necessary to discuss the effect of anti-TNF and immunosuppressive therapy on the effcacy of mesenchymal stem cell treatment for perianal fistula in future trials, in order to optimize treatment strategies in perianal fistula patients and reduce the economic burden of patients. In the future, it will be interesting to assess the safety and feasibility of injection of fibrin glue combined with mesenchymal stem cells in perianal fistula.

Introduction: Acne is a prevalent inflammatory skin condition that occurs in adolescents and can persist into adulthood. CircRNA has been reported to be widely involved in a variety of human diseases. However, the regulatory mechanism of hsa_circ_0001445 in acne has rarely been reported. The purpose is to research the role of hsa_circ_0001445 in acne-induced inflammation and its molecular regulatory mechanism to provide a foundation for the exploration of acne-targeting drugs.

Material and methods: We used the GEO, starBase, and GeneCards databases for bioinformatics analysis. The binding sequences of miR-1298-5p and hsa_circ_0001445 or ESR1 mRNA were predicted by the Circular RNA Interactome or starBase database. Double luciferase reporting assay was applied to verify the regulatory relationship between hsa_circ_0001445, miR-1298-5p, and ESR1. RT-qPCR was used to detect levels of hsa_circ_0001445, miR-1298-5p, and ESR1 mRNA. The secretion levels of interleukin (IL)-6, IL-8, and tumor necrosis factor α (TNF-α) were measured using an ELISA kit.

Results: The luciferase activity was weakened by miR-1298-5p mimics in human keratinocytes and sebocytes transfected with wild-type (wt)-circ1445 and wt-ESR1, respectively. Moreover, the overexpression of hsa_circ_0001445 reduced the miR-1298-5p level and reversed the elevation of IL-6, IL-8, and TNF-α levels in Bio-C. acnes-stimulated keratinocytes and sebocytes. In turn, transfection of miR-1298-5p mimics partially eliminated the inflammatory inhibition of hsa_circ_0001445, which was reversed by co-transfection of pcDNA-ESR1.

Conclusions: Hsa_circ_0001445 improved acne inflammation via sponging miR-1298-5p targeting ESR1.