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关键词： pertussis vaccine   Treg cell   T-RM cell   Th17 cell   IL-10  

摘要： Tissue-resident memory T (T-RM) cells play a key role in sustained protective immunity against Bordetella pertussis infection of the nasal mucosa. Current alum-adjuvanted acellular pertussis (aP) vaccines protect against severe pertussis disease but fail to prevent nasal infection with B. pertussis. Here we demonstrate that immunization of mice with an aP vaccine failed to generate respiratory T-RM cells, but did induce antigen-specific CD4(+) Treg cells that expressed Foxp3, CD49b, PD-1 and LAG-3, and CD8(+) Treg cells that expressed CD122, PD-1, and IL-10. B. pertussis-specific CD4(+) and CD8(+) T cell lines established from aP-immunized mice expressed the regulatory markers and suppressed activation of Th1 and Th17 cells. Blockade of IL-10 signaling during aP immunization or B. pertussis challenge promoted the induction of IL-17-secreting CD4(+) T-RM responses and enhanced bacterial clearance from the nose. Addition of the adjuvant LP-GMP, comprising TLR2 and STING agonists, to the aP vaccine and delivery by the nasal route promoted the induction of antigen-specific IL-17-producing CD4(+) T-RM cells and enhanced vaccine efficacy. Our findings demonstrate that aP vaccines suppress the induction of protective T-RM cells in part through the induction of CD4(+) and CD8(+) Treg cells, which can be overcome using a potent adjuvant and delivery of the vaccine intranasally.

关键词： Leiomyoma   Uterin fibroid   Polymorphism   ERS-1   IL-8   ICAM-1   TNFAIP2  

摘要： Objective: In this study, we aimed to investigate the difference between ICAM-1, IL-8, and ER-alpha gene polymorphisms and the effects of the formation of leiomyomas by measuring serum levels of IL-8 and ICAM-1 in uterine leiomyoma and control patients. Study Design. The roles of ERS-1, TNSFIP2, ICAM-1, and IL-8 gene polymorphisms in leiomyoma development were investigated using TaqMan SNP genotyping assay. In addition, serum IL-8 and ICAM-1 levels of leiomyoma and control group individuals were measured using the ELISA method. The sample included in the study consisted of 75 people diagnosed with uterine leiomyoma (leiomyoma group) and 75 healthy volunteers without ovarian pathology (control group) who came to Sivas Cumhuriyet University Medical Faculty Gynaecology and Obstetrics Clinic. Results: TNFAIP2 rs8126, ICAM-1 rs5498 and ESR-1 rs17847075 polymorphisms were not associated with leiomyoma disease. In addition, individuals carrying heterozygous genotypes of ESR-1 rs9322331 (p = 0.01, OR = 2.4), IL-8 rs4073 (p = 0.02, OR = 2.4) and IL-8 rs2227306 (p = 0.01, OR = 2.246) polymorphisms may be at risk for leiomyoma. Similarly, mutant alleles of ESR-1 rs9322331 (p = 0.005, OR = 2.172), IL-8 rs4073 (p = 0.01, OR = 2.204) and IL-8 rs2227306 (p = 0.004, OR = 2.2) polymorphisms were found to be risk alleles. Furthermore, it was observed that IL-8 serum levels increased more in the leiomyoma group (1.83 f 0.4 pg/mL) compared to the control group (1.02 f 0.2 pg/mL). Likewise, a significant decrease in ICAM-1 levels was found in the leiomyoma group (1595.5 f 80 ng/mL) compared to the control group (2939.3 f 104 ng/mL). Conclusion: In this context, it was concluded that polymorphisms of IL-8 and ESR-1 genes, which are thought to be risk factors in leiomyoma harvests, and factors affecting IL-8 and ICAM-1 expression should be further investigated.

摘要： Excessive inflammation and cytokine release are hallmarks of severe COVID-19. Certain programmed cell death processes can drive inflammation, however, their role in the pathogenesis of severe COVID-19 is unclear. Pyroptosis is a pro-inflammatory form of regulated cell death initiated by inflammasomes and executed by the pore-forming protein gasdermin D (GSDMD). Using an established mouse adapted SARS-CoV-2 virus and a panel of gene-targeted mice we found that deletion of the inflammasome (NLRP1/3 and the adaptor ASC) and pore forming proteins involved in pyroptosis (GSDMA/C/D/E) only marginally reduced IL-1 beta levels and did not impact disease outcome or viral loads. Furthermore, we found that SARS-CoV-2 infection did not trigger GSDMD activation in mouse lungs. Finally, we did not observe any difference between WT animals and mice with compound deficiencies in the pro-inflammatory initiator caspases (C1/11/12-/-). This indicates that the classical canonical and non-canonical pro-inflammatory caspases known to process and activate pro-IL-1 beta, pro-IL-18 and GSDMD do not substantially contribute to SARS-CoV-2 pathogenesis. However, the loss of IL-1 beta, but not the absence of IL-18, ameliorated disease and enhanced survival in SARS-CoV-2 infected animals compared to wildtype mice. Collectively, these findings demonstrate that IL-1 beta is an important factor contributing to severe SARS-CoV-2 disease, but its release was largely independent of inflammasome and pyroptotic pathways.

关键词： Chikungunya   Cytokine   Chemokine   Chronic chikungunya arthritis  

摘要： Background: Cytokines and chemokines play a crucial role in orchestrating the immune response to chikungunya virus (CHIKV) infection, influencing disease course and outcome. Although significant efforts have been made to understand the cytokine signatures associated with CHIKV infection, the identification of specific cytokine biomarkers across different disease stages remains incomplete. Material and method: We have assessed CHIKV-specific cytokine, chemokine profiles of 17 analytes in 50 acute chikungunya patients, 31 chronic chikungunya arthritis patients, 30 recovered individuals, and 23 healthy controls. The cytokine and chemokines were measured in the supernatant of PBMCs stimulated in vitro with inactivated chikungunya virus. Results: It was observed that chronic chikungunya arthritis patients exhibited significantly higher levels of IL1(3, IL-6, and GM-CSF compared to all other groups. MCP-1 levels were elevated in patient groups compared to recovered and control individuals. IL-1(3 emerged as a potential biomarker for chronic chikungunya arthritis based on ROC analysis. A negative correlation between IFN-gamma levels and CHIKV load was observed in acute patients, suggesting its antiviral role. IL-12 levels were higher in recovered individuals compared to all other groups, while IFN-gamma levels were elevated in recovered individuals compared to acute patients. Conclusion: Our findings highlight IL-1(3 as a potential biomarker for chronic chikungunya arthritis and suggest that GM-CSF inhibition could serve as a therapeutic intervention for disease-associated chronic inflammation. The observed co-regulation of IL-12 and IFN-gamma in recovered individuals needs further investigation into their role in disease resolution. These insights provide a deeper understanding of the immunopathogenesis of CHIKV infection and may contribute in future diagnostic and therapeu tic strategies.

关键词： coding change   HLA-A*03:505   NGS  

摘要： HLA-A*03:505 contains a single nucleotide substitution at nucleotide position 236 (GAG to GCG).

关键词： italic>C*15:271N   HLA-C   NGS   organ transplantation  

摘要： HLA-C*15:271N differs from HLA-C*15:02:01:01 by an insertion in exon 3 leading to a premature termination codon.

关键词： HLA   italic>HLA-A*03:512   novel allele   sequencing-based typing  

摘要： HLA-A*03:512 differs from HLA-A*03:01:01:01 by one nucleotide substitution in codon 238 in exon 4.

关键词： Congenital idiopathic megaoesophagus   risk-test   MCHR2gene   White Swiss shepherd   Berger Blanc Suisse  

摘要： Gene tests play an important role for controlling monogenetic diseases because they reveal a genotype for each tested dog and thereby allow for the selection of animals with a lower genetic burden. For some complex inherited diseases and anomalies so called risk-tests are available and may support the selection of breeding animals. They analyze DNA-sequence variants which render a higher risk for carriers to develop a disease or anomaly. The usefulness of a risk-test for congenital idiopathic megaoesophagus (CIMtest) in German shepherds was analyzed in the closely related breed of White Swiss shepherds. The results showed clearly that the CIM-test in this breed is almost not informative, and a selection would probably not reduce the prevalence but only lower the genetic variability. Breeders and owners should be informed accordingly.

关键词： Bullous pemphigoid   Carbamazepine   Clinical utility   DPP-4 inhibitor   Salazosulfapyridine  

摘要： The association of human leukocyte antigen (HLA) with the risk of drug-induced skin eruptions has been extensively studied. The sensitivity of the association of specific HLA alleles with drug eruptions ranges from approximately 50 to 100%, indicating a significant influence of HLA alleles on the risk of developing such reactions. Consequently, HLA testing holds substantial clinical potential as a genetic diagnostic tool to avoid drug eruptions. For instance, when prescribing drugs like carbamazepine and lamotrigine, which are known to cause severe drug eruptions, preemptive HLA genetic testing can help predict an individual's risk. This approach enables clinicians to reduce the overall incidence of drug eruptions by selecting alternative therapeutic agents or adjusting dosages based on the results of HLA genetic testing. (c) 2025 Japanese Society of Allergology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).