Immunologic Research最新文献

{"title":"Electrical vagus nerve stimulation is a promising approach to reducing pulmonary complications after an esophagectomy: an experimental rodent model.","authors":"Henricus J B Janssen, Tessa C M Geraedts, Laura F C Fransen, Ingrid van Ark, Thea Leusink-Muis, Gert Folkerts, Johan Garssen, Jelle P Ruurda, Grard A P Nieuwenhuijzen, Richard van Hillegersberg, Misha D P Luyer","doi":"10.1007/s12026-024-09523-3","DOIUrl":"https://doi.org/10.1007/s12026-024-09523-3","url":null,"abstract":"<p><p>After esophagectomy, an imbalanced inflammatory response increases the risk of postoperative morbidity. The vagus nerve modulates local and systemic inflammatory responses, but its pulmonary branches are transected during esophagectomy as part of the oncological resection, which may account for the high incidence of postoperative (pulmonary) complications. This study investigated the effect of electrical vagus nerve stimulation (VNS) on lipopolysaccharide (LPS)-induced lung injury in rats. Rats (n = 60) were randomly assigned to a non-vagotomy or cervical vagotomy group, with VNS or without (NOSTIM). There were four non-vagotomy groups: NOSTIM and bilateral VNS with 100, 50, or 10 µA. The four vagotomy groups were NOSTIM and VNS with fixed amplitude (50 µA) bilaterally before (VNS-50-before) or after bilateral vagotomy (VNS-50-after), or unilaterally (left) before ipsilateral vagotomy (VNS-50-unilaterally). LPS was administered intratracheally after surgery. Pulmonary function, pro-inflammatory cytokines in serum, broncho-alveolar lavage fluid (BALF), and histopathological lung injury (LIS) were assessed 180 min post-procedure. In non-vagotomized rats, neutrophil influx in BALF following intra-tracheal LPS (mean 30 [± 23]; P = 0.075) and LIS (mean 0.342 [± 0.067]; P = 0.142) were similar after VNS-100, compared with NOSTIM. VNS-50 reduced neutrophil influx (23 [± 19]; P = 0.024) and LIS (0.316 [± 0.093]; P = 0.043). VNS-10 reduced neutrophil influx (15 [± 6]; P = 0.009), while LIS (0.331 [± 0.053]; P = 0.088) was similar. In vagotomized rats, neutrophil influx (52 [± 37]; P = 0.818) and LIS (0.407 [SD ± 0.037]; P = 0.895) in VNS-50-before were similar compared with NOSTIM, as well as in VNS-50-after (neutrophils 30 [± 26]; P = 0.090 and LIS 0.344 [± 0.053]; P = 0.073). In contrast, VNS-50-unilaterally reduced neutrophil influx (26 [± 10]; P = 0.050) and LIS (0.296 [± 0.065]; P = 0.005). Systemic levels of cytokines TNF-α and IL-6 were undetectable in all groups. Pulmonary function was not statistically significantly affected. In conclusion, VNS limited influx of neutrophils in lungs in non-vagotomized rats and may attenuate LIS. Unilateral VNS attenuated lung injury even after ipsilateral vagotomy. This effect was absent for bilateral VNS before and after bilateral vagotomy. It is suggested that the effect of VNS is dependent on (partially) intact vagus nerves and that the level of the vagotomy during esophagectomy may influence postoperative pulmonary outcomes.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating CD8 + LGALS9 + T Cell Population Exhibiting Low Cytotoxic Characteristics are Decreased in Patients with Systemic Lupus Erythematosus.","authors":"Qi Li, Guochong Wang, Zihang Yuan, Rui Kang, Yaxin Li, Ayibaota Bahabayi, Ziqi Xiong, Zhonghui Zhang, Chen Liu","doi":"10.1007/s12026-024-09522-4","DOIUrl":"https://doi.org/10.1007/s12026-024-09522-4","url":null,"abstract":"<p><p>LGALS9, also known as Galectin-9 and a member of the β-galactosidase family, plays a crucial role in immune regulation. However, its expression and function in CD8 T cells, as well as its association with cytotoxic T lymphocytes (CTL), remain unclear. This study aims to investigate LGALS9 expression patterns in human circulating CD8 T lymphocytes and elucidate its clinical significance in Systemic Lupus Erythematosus (SLE). Blood samples from 56 healthy controls and 50 new-onset SLE patients were collected. Flow cytometry was utilized to analyze LGALS9 expression in circulating CD8 T lymphocytes via intracellular staining. Compared to LGALS9 + CD8 + T cells, LGALS9-CD8 + T cells showed increased secretion of Granzyme B (GZMB) and Perforin, along with elevated expression levels of GPR56, CX3CR1, KLRD1, KLRF1, PD1, and CD29. A higher proportion of Tn (naive T cells) and TCM (central memory T cells) showed LGALS9 positivity, compared to TEM (effector memory T cells) and TEMRA (terminally differentiated effector memory T cells re-expressing CD45RA). Clinically, the downregulation of LGALS9 expression was significant in SLE patients. LGALS9 + CD8 + T cells exhibited an Area Under the Curve (AUC) of 0.6916, while CX3CR1 + in LGALS9 + CD8 + T cells had an AUC of 0.6478, and KLRF1 + had an AUC of 0.6419, for distinguishing SLE from healthy individuals. In conclusion, CD8 + LGALS9 + T cells display characteristics of low cytotoxicity, and their reduction is evident in SLE patients, potentially implicating them in SLE pathogenesis and providing diagnostic assistance.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 in Systemic Lupus Erythematosus patients treated with belimumab: a retrospective clinical study.","authors":"Yinlan Wu, Yanhong Li, Tong Wu, Deying Huang, Jianhong Wu, Weihua Zhang, Xuejun Jiang, Chaoqiong Yao, Xiuping Liang, Lu Cheng, Zehui Liao, Fang Xu, Chunyu Tan, Yi Liu, Martin Herrmann","doi":"10.1007/s12026-023-09449-2","DOIUrl":"10.1007/s12026-023-09449-2","url":null,"abstract":"<p><strong>Background: </strong>Routine use of immunosuppressive agents in systemic lupus erythematosus (SLE) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially increases the risk of adverse outcomes. belimumab, a monoclonal antibody for the treatment of SLE, remains untested for its specific impact on coronavirus disease 2019 (COVID-19) symptoms in these patients. Here, this research investigated the effect of belimumab on COVID-19 symptoms in SLE patients infected with SARS-CoV-2.</p><p><strong>Methods: </strong>This study enrolled SLE patients who underwent treatment with belimumab. After thorough screening based on the inclusion and exclusion criteria, data pertaining to COVID-19 for both the participants and their cohabitants were obtained through telephone follow-up. The potential impact of belimumab on COVID-19 was evaluated by comparing COVID-19 symptoms and medication use across various groups to investigate the association between belimumab treatment and COVID-19 in SLE.</p><p><strong>Results: </strong>This study involved 123 SLE patients, of whom 89.4% tested positive for SARS-CoV-2. Among cohabitants of SLE patients, the SARS-CoV-2 positive rate was 87.2% (p = 0.543). Patients treated with belimumab exhibited a lower incidence of multiple COVID-19 symptoms than their cohabitating counterparts (p < 0.001). This protective effect was found to be partially related to the time of last belimumab administration. Among those with COVID-19, 30 patients opted to discontinue their anti-SLE drugs, and among them, 53% chose to discontinue belimumab. Discontinuing drugs did not increase the risk of hospitalization due to SARS-CoV-2 infection.</p><p><strong>Conclusion: </strong>This study concluded that treatment with belimumab did not increase susceptibility to COVID-19 and beneficially alleviated the symptoms of COVID-19.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conventional Tregs in treatment-naïve rheumatoid arthritis are deficient in suppressive function with an increase in percentage of CXCR3 and CCR6 expressing Tregs.","authors":"Vallayyachari Kommoju, Christina Mary Mariaselvam, Sree Nethra Bulusu, Chengappa Kavadichanda Ganapathy, Prakash Babu Narasimhan, Molly Mary Thabah, Vir Singh Negi","doi":"10.1007/s12026-023-09444-7","DOIUrl":"10.1007/s12026-023-09444-7","url":null,"abstract":"<p><p>In rheumatoid arthritis (RA), immune homeostasis is maintained by T regulatory cells (Tregs) that in an inflammatory milieu can change towards T-helper-like phenotypes (Th-like Tregs). Our aim was to examine the phenotypic and functional characteristics of CD4⁺CD25⁺CD127^lo/- Tregs, Th-like Tregs and T effector (Teff) cells in the peripheral blood (PB) and synovial fluid (SF) of treatment-naïve early RA, as compared to osteoarthritis (OA) and healthy control (HC) peripheral blood. Frequencies of Tregs, CXCR3, CCR6 expressing Tregs (Th-like Tregs), and Teff cells were analyzed using flow cytometry in RA (n = 80), OA (n = 20), and HC (n = 40). Cytokine concentrations of the respective T cell subsets in plasma and SF were measured using flow cytometric bead array. Tregs sorted from RA and HC PB using magnetic beads were analyzed for functional capacities by CFSE proliferation assay and FOXP3 gene expression using real-time PCR. We observed that the frequencies of Th17 cells in PB and SF were significantly higher in RA when compared to HC, whereas Tregs were lower in PB and high in SF compared to HC and OA respectively. Th1- and Th17-related pro-inflammatory cytokines IL12p70, INF-γ, TNF-α, and IL-6, and IL-17A were significantly higher in the plasma and SF of RA. Tregs expressing CXCR3 (Th1-like Tregs) and CCR6 (Th17-like Treg) were significantly higher in PB and SF of RA compared to controls and was positively associated with seropositivity and disease activity. Treg cells isolated from peripheral blood of RA showed decreased function and reduced FOXP3 gene expression compared to HC. In our study, we have demonstrated higher frequencies of Th1 and Th17 cells and increased circulatory and SF pro-inflammatory cytokines (IL12P70, INF-γ, IL-6, IL-17A, and TNF-α) in RA. This inflammatory milieu might alter total Tregs frequencies and influence conversion of Tregs into Th-like Tregs.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation profiling of labial salivary gland tissues revealed hypomethylation of B-cell-related genes in primary Sjögren's syndrome.","authors":"Jayakanthan Kabeerdoss, Prabavathi Devarajalu, Pulukool Sandhya","doi":"10.1007/s12026-024-09453-0","DOIUrl":"10.1007/s12026-024-09453-0","url":null,"abstract":"<p><p>The objective of this epigenetic study was to investigate the cellular proportions based on DNA methylation signatures and pathways of differentially methylated genes in labial salivary gland (LSG) tissues of individuals with Sjögren's syndrome (SS). Two methylation array datasets from the Gene Expression Omnibus repository (GSE166373 and GSE110007) were utilized, consisting of 159 LSG tissues from 77 SS cases and 82 non-SS controls. The raw data underwent analysis using the Chip Analysis Methylation Pipeline (ChAMP) in R statistical tool, which identified differential methylation probes and regions. The EpiDISH and minfi packages in R were employed to identify proportions of epithelial cells, fibroblasts, and immune cells, as well as immune cell subsets. The results showed that proportions of immune cells were increased, while proportions of epithelial cells and fibroblasts were significantly decreased in the LSG of individuals with SS compared to non-SS controls. Specifically, proportions of B-cells and CD8 T-cells were increased, while CD4 T-cells, Treg, monocytes, and neutrophils were decreased in the LSG of individuals with SS. Pathway analysis indicated that genes involved in immune responses to Epstein-Barr virus infection were significantly hypomethylated in SS, and gene set enrichment analysis highlighted the hypomethylation of genes involved in the somatic recombination of immune receptors in SS. Additionally, Disease Ontology analysis showed enriched pathways related to multiple myeloma, arthritis, and the human immunodeficiency virus. The study also revealed significant hypomethylation of the WAS gene on chromosome X in LSG tissues of individuals with SS. Overall, the findings suggest an increased proportion of B-cells and genes related to B-cell function, as well as hypomethylation of genes involved in immune responses and immune receptor recombination, in LSG tissues of individuals with SS compared to non-SS controls.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discouraging Non-ELISA antiphospholipid antibody assays in antiphospholipid syndrome classification may hinder clinical research.","authors":"Xiaochun Susan Zhang, Nicola Bizzaro, Anne E Tebo, Vijayalakshmi Nandakumar, Maria Infantino, Teresa Carbone, Xavier Bossuyt, Jan Damoiseaux","doi":"10.1007/s12026-023-09443-8","DOIUrl":"10.1007/s12026-023-09443-8","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APLAID complicated with arrhythmogenic dilated cardiomyopathy caused by a novel PLCG2 variant.","authors":"Tianjiao Wang, Xinyu Wang, Yiqun Teng, Lifang Wu, Feng Zhu, Danjie Ma, Hua Wang, Xiaolin Liu","doi":"10.1007/s12026-024-09455-y","DOIUrl":"10.1007/s12026-024-09455-y","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection.","authors":"Yue Chen, Jinlin Liu, Diao Yu","doi":"10.1007/s12026-023-09447-4","DOIUrl":"10.1007/s12026-023-09447-4","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monophosphoryl lipid A as a co-adjuvant in methicillin-resistant Staphylococcus aureus vaccine development: improvement of immune responses in a mouse model of infection.","authors":"Mehdi Mirshekar, Setareh Haghighat, Zahra Mousavi, Amir Hossein Abdolghaffari, Mohammad Hossein Yazdi","doi":"10.1007/s12026-024-09456-x","DOIUrl":"10.1007/s12026-024-09456-x","url":null,"abstract":"<p><p>To increase the effectiveness of methicillin-resistant Staphylococcus aureus vaccines (MRSA), a new generation of immune system stimulating adjuvants is necessary, along with other adjuvants. In some vaccines, monophosphoryl lipid A (MPLA) as a toll-like receptor 4 agonist is currently used as an adjuvant or co-adjuvant. MPLA could increase the immune response and vaccine immunogenicity. The current investigation assessed the immunogenicity and anti-MRSA efficacy of recombinant autolysin formulated in MPLA and Alum as co-adjuvant/adjuvant. r-Autolysin was expressed and purified by Ni-NTA affinity chromatography and characterized by SDS-PAGE. Then, the vaccine candidate formulation in MPLAs and Alum was prepared. To investigate the immunogenic responses, total IgG, isotype (IgG1 and IgG2a) levels, and cytokines (IL-4, IL-12, TNF-α, and IFN-γ) profiles were evaluated by ELISA. Also, the bacterial burden in internal organs, opsonophagocytosis, survival rate, and pathobiology changes was compared among the groups. Results demonstrated that mice immunized with the r-Autolysin + Alum + MPLA Synthetic and r-Autolysin + Alum + MPLA Biologic led to increased levels of opsonic antibodies, IgG1, IgG2a isotype as well as increased levels of cytokines profiles, as compared with other experimental groups. More importantly, mice immunized with MPLA and r-Autolysin exhibited a decrease in mortality and bacterial burden, as compared with the control group. The highest level of survival was seen in the r-Autolysin + Alum + MPLA Synthetic group. We concluded that both MPLA forms, synthetic and biological, are reliable candidates for immune response improvement against MRSA infection.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A ubiquitin-proteasome system-related signature to predict prognosis, immune infiltration, and therapy efficacy for breast cancer.","authors":"Xiao Liu, Meihuan Wang, Qian Wang, Huawei Zhang","doi":"10.1007/s12026-023-09440-x","DOIUrl":"10.1007/s12026-023-09440-x","url":null,"abstract":"<p><p>The ubiquitin-proteasome system (UPS) is an essential regulatory system for maintaining homeostasis, and its dysfunction may cause various diseases. The activity of proteasome and ubiquitin-conjugating enzymes has been found to be greatly increased in breast cancer (BC), indicating that the heterogeneity of UPS may be related to the progression of BC. Gene data was obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases and performed in multiple algorithms to construct a UPS-related signature for BC. Patients in the UPS low-risk group had greater overall and recurrence-free survival probability than those in the UPS high-risk group. This signature was closely associated with functional enrichment. Some high metabolism-related pathways were more active in the UPS high-risk group. The UPS low-risk group had more abundant anti-tumor immune cells, while in the UPS high-risk group, immunosuppressive cells were dominant. More importantly, we found that the UPS low-risk group was more sensitive to immunotherapy, while the UPS high-risk group responded better to radiotherapy. Drug sensitivity analysis identified more effective chemotherapy drugs in different UPS-related risk groups. This UPS-related signature may serve as a novel biomarker and independent prognostic factor for BC. It can effectively predict prognosis, immune infiltration, and therapy efficacy, providing new strategies for individualized treatment.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}