课程文献中心 更多>>

关键词： Interleukin 6   Interleukin 6 receptor   Nibea albiflora   Poly (I:C)   Vibrio alginolyticus   Vibrio parahaemolyticus  

摘要： Interleukin 6 (IL-6) is one of the cytokines found to be multifunctional and biologically effective, regulating immune and inflammatory response by interacting with receptors to transmit signals. In this study, the full-length cDNAs of IL-6 (named as NaIL-6) and its receptors IL-6R and gp130 (named as NaIL-6Rα and NaIL-6Rβ) of Nibea albiflora were acquired and they possessed the typical symbolic motifs similar to its teleost orthologues in multiple sequence comparisons. The phylogenetic trees showed that NaIL-6 and its receptors clustered with their counterparts in bony fish, and had the closest affinity to Larimichthys crocea. Real-time PCR indicated that NaIL-6, NaIL-6Rα and NaIL-6Rβ were widely expressed in different tissues, among which NaIL-6 was highly expressed in the liver, NaIL-6Rα showed the highest expression in the kidney and NaIL-6Rβ was reflected in the liver. Following stimulation by Vibrio parahaemolyticus, Vibrio alginolyticus, or Polyinosinic-polycytidylic acid (Poly (I:C)) infection, the mRNA expression of all three genes were greatly up-regulated over time. The cell localization analysis showed that NaIL-6 distributed in cytoplasm and cell membrane, and NaIL-6Rα located on the cell membrane. After co-transfection of NaIL-6- mCherry and NaIL-6Rα-EGFP, they co-expressed as orange at the same position for their possibility of spatial interactions on the cellular membrane. By GST-Pull down with the purified target proteins, the association between NaIL-6-His and NaIL-6Rα-GST was confirmed, which may be utilized for further functional study. Taken together, the results indicated that the biological functions of NaIL-6 and its receptors NaIL-6Rα and NaIL-6Rβ involved in the immunologic mechanism in ***, which would provide a basis for the research of immune functions and signaling pathway of IL-6 and its receptors in fish.

摘要： We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated. We show that HSP60 chaperone positively regulates the protein levels for multiple glutaminolysis- and FAO-related enzymes, thereby actively fueling the levels of cellular alpha-ketoglutarate (αKG) and related mitochondrial ATP-dependent antiviral T cell immunity in both CD4 and CD8 TM. Finally, we provide a way to rescue defective ATP generation in mitochondria and dependent effector functions in virus-specific TM including anti-HIV-1 protective responses, when HSP60 expression is impaired after TCR engagement in patients, in the form of dimethyl 2-oxoglutarate (DMKG) supplementation.

关键词： CP: Immunology   CP: Microbiology   ORF9b   SARS-CoV-2   autophagy   cell-autonomous interferon response   coronavirus   innate immune signaling   mitophagy   viral evolution  

摘要： SARS-CoV-2 emerged, and continues to evolve, to efficiently infect humans worldwide. SARS-CoV-2 evades early innate recognition, interferon signaling occurring only in bystander cells. How the virus continues to evolve in the face of innate responses has important consequences, but the pathways involved are incompletely understood. Here, we find that autophagy genes regulate innate immune signaling, impacting the basal set point of interferons and, thus, permissivity to infection. Mechanistically, autophagy (mitophagy) genes negatively regulate MAVS, and this low basal level of MAVS is efficiently antagonized by SARS-CoV-2 ORF9b, blocking interferon activation in infected cells. However, loss of autophagy increased MAVS and overcomes ORF9b-mediated antagonism. This has driven the evolution of SARS-CoV-2 to express more ORF9b, allowing SARS-CoV-2 to replicate under conditions of increased MAVS signaling. Altogether, we find a critical role of mitophagy in the regulation of innate immunity and uncover an evolutionary trajectory of SARS-CoV-2 ORF9b to overcome host defenses.

关键词： IL28A   IL28B   IL28RA   Apoptosis   AMI  

摘要： While current coronary intervention therapies and surgical bypass procedures are widely utilized, the treatment of acute myocardial infarction (AMI) in the elderly continues to pose significant challenges. Following AMI, the body's immune system is activated, resulting in the release of inflammatory mediators that exacerbate myocardial damage. Interleukin 28A (IL28A) and interleukin 28B (IL28B) may play a role in immune regulation post-AMI by specifically binding to interleukin 28 receptor alpha (IL28RA). However, the precise underlying mechanisms remain incompletely understood. This study aims to investigate the levels of IL28A and IL28B following AMI, as well as the protective effects of inhibiting IL28RA expression in the context of AMI and its potential mechanisms. We analyzed serum samples from 55 patients with AMI and 41 control individuals using ELISA to evaluate the levels of IL28A and IL28B, as well as to assess their correlation with the clinical parameters of the patients. Additionally, we established a mouse model of AMI and employed intramyocardial injection of lentivirus to knock down IL28RA in the myocardium. Echocardiography was utilized to compare structural and functional changes, while HE staining was conducted to analyze the infarct area and assess changes in myocardial tissue and cell morphology. The expressions of IL28A, IL28B, IL28RA, and JAK1/STAT1 pathway-related proteins in the infarct area were compared through immunofluorescence and Western blot analysis. Finally, TUNEL staining and the BAX/Bcl2 ratio were utilized to evaluate cardiomyocyte apoptosis. The study demonstrated that serum IL28A levels in patients with AMI were significantly elevated compared to those in normal controls, whereas IL28B levels were significantly reduced. Additionally, both IL28A and IL28B levels exhibit a linear relationship with high-density lipoprotein (HDL) and body mass index (BMI). In a mouse model, cardiac function deteriorated and ventricular structural c

关键词： Immunology   Cell biology   Transcriptomics  

摘要： Natural killer (NK) cell activity is influenced by cytokines and microenvironment factors, resulting in remarkably diverse functions, by contributing to inflammatory responses or serving as rheostats of adaptive immunity. Using single cell RNA sequencing (scRNA-seq), we identified a TGFb1highCD56brightNK cell population associated with hematopoietic stem cell transplant recipients protected from acute graft-versus-host disease (GVHD). We further define a role for the combination of interleukin-2 (IL-2) and transforming growth factor R1 (TGF-R1) in promoting a regulatory phenotype in NK cells. "Induced"regulatory NK cells produce high amounts of TGF-R1, inhibited T cells, could promote naive T cells differentiation into regulatory T cells, and exhibited a unique transcriptional program that includes expression of IKZF2 (HELIOS) and ZNF683 (HOBIT). This phenotype was not stable, and "induced"regulatory NK cells lost the ability to secrete TGF-R1 upon exposure to different cytokines. These findings define protective CD56brightNK cells post-hematopoietic stem cell transplantation, and demonstrate the combination of IL-2 and TGF-R1 promotes regulatory activity in NK cells.

关键词： Highlights   Biological sciences   Immune response   Immune system   Immunology   Natural  

摘要： Sepsis, a leading cause of mortality in intensive care units worldwide, lacks effective treatments for advanced-stage sepsis. Therefore, understanding the underlying mechanisms of this disease is crucial. This study reveals that invariant natural killer T (iNKT) cells have an opposing role in the progression of sepsis by suppressing regulatory T (Treg) cell differentiation and function. The activation of iNKT cells by a-Galcer enhances interferon (IFN)-y production. Blocking antibodies or transferring IFN-y-deficient iNKT cells demonstrates that iNKT cells inhibit Treg differentiation through IFN-y production. Additionally, iNKT cell-mediated Treg inhibition prevents secondary infection caused by Listeria monocytogenes during the post-septic phase. The transcriptomic analysis of Treg cells further reveals that the suppressive function of Tregs is impaired by iNKT cells. Finally, we demonstrate that iNKT cells inhibit Treg differentiation in an Nr4a1-dependent manner. Our data uncover the dual function of iNKT cells in sepsis progression and provide a potential treatment target for this adverse long-term outcome induced by sepsis.

关键词： Liver cancer surgery   Liver function   Pro-inflammatory cytokines   Stored autologous blood transfusion  

摘要： PURPOSE:This study aim is to evaluate the application of stored autologous blood transfusion in liver cancer surgery and explore its impact on postoperative changes in inflammatory factors and liver function recovery. METHOD:The study used a control group (CG) design and included 150 patients who underwent liver cancer surgery. While the observation group (OG) got autologous blood that had been preserved, the CG had a standard allogeneic blood transfusion. Examine the variations between the CG and the OG using the following measures: prior to, during, and following surgery contrast MELD score, blood routine indicators, pro-inflammatory cytokine levels. RESULT:MELD ratings, IL-1, IL-6, TNF-α levels, and preoperative blood routine indicators did not differ between the observation and CGs (p > 0.05). However, the blood routine indicators in the OG were lower than those in the CG on the first day following surgery (p < 0.05); seven days following surgery, there was no significant difference among the experiment participants (p > 0.05). In the meanwhile, the postoperative OG's levels of IL-1, IL-6, TNF-α, and HAF were lower than those of the CG (p < 0.05). The PVF of the OG was lower than the CG on the first day following surgery (p < 0.05), but on the seventh day following surgery, there was no discernible difference between the experiment's participants (p > 0.05). CONCLUSION:The research outcomes showcase that stored autologous blood transfusion can reduce the levels of inflammatory factors after surgery and promote the recovery of liver function;Research suggests important references for further understanding the application and mechanism of stored autologous blood transfusion, and provide a basis for personalized treatment and recovery of liver cancer patients undergoing surgery.

关键词： 干眼   2型糖尿病   Caspase-1   炎症因子  

摘要： 目的 干眼是糖尿病的眼部常见并发症。电针治疗糖尿病干眼临床有效，但其机制尚不清楚。本研究旨在揭示电针如何调节Caspase-1及其下游IL-1β和IL-18，改善2型糖尿病干眼大鼠角膜炎症，从而缓解2型糖尿病干眼大鼠眼表体征的潜在机制。方法 实验采用1%链脲佐菌素腹腔注射建立2型糖尿病干眼大鼠模型，并设立空白组、模型组、电针组、假针组、氟米龙组。选取睛明、攒竹、丝竹空、太阳、瞳子髎电针干预大鼠，造模前、造模后、治疗后检测随机血糖、泪膜破裂时间、角膜荧光素钠染色、酚红棉线实验、角膜机械知觉阈值及瞬目次数观察大鼠全身及眼表情况。采用HE染色法观察大鼠角膜形态。采用免疫组织化学法、Western blot、RT-PCR法测定角膜组织中Caspase-1、IL-1β和IL-18的表达水平。结果 电针可提高2型糖尿病干眼大鼠的泪膜破裂时间、泪液分泌量、角膜敏感性，促进角膜上皮修复，并抑制角膜组织中Caspase-1及其下游IL-1β和IL-18的表达水平。结论 电针对2型糖尿病干眼大鼠眼表的治疗作用，与其抑制角膜中Caspase-1及其下游IL-1β和IL-18表达的抗炎效应有关。