课程文献中心 更多>>

摘要： Long-lived memory B cells developing from germinal centers (GCs) are important contributors to protective immunity. In this issue of Immunity, Luo et al. report that during primary responses, T cell-derived interleukin-9 potentiates differentiation of GC memory precursors into functional memory B cells in a manner dependent on the transcriptional regulator ZBTB18.

关键词： T regulatory cells   autoimmunity   experimental autoimmune encephalomyelitis   interleukin-2  

摘要： Experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin basic protein (MBP) is a self-limiting disease model of multiple sclerosis. CD4CD25Foxp3T cells play a role in limiting autoimmune disease but treatment with antigen naïve CD4CD25 cells does not reduce EAE. This study examined if in vitro activation by MBP and rIL-2 induced CD4CD25Foxp3 cells that could inhibit EAE. Culture of CD4CD8CD25cells from naïve rats with MBP and rIL-2 induced activated Treg that reduced the severity of clinical EAE and infiltration of CD8T cells and macrophage into brain stem. CD4CD25T cells activated by an irrelevant autoantigen and rIL-2 did not suppress EAE. Resting CD4CD25T cells activated by autoantigen and rIL-2 have mRNA for Infgr, Il12rb2, Il5 but not Tbet, Gata3, Ilr5ra or Ifng. These changes in mRNA expression are the markers of Ts1 cells. A proportion of CD4CD8CD25 cells activated by MBP/rIL-2 were induced to express CD8α, CD8β and CD62L. Depletion of CD4CD8αCD25 cells removed the capacity of MBP and rIL-2 activated CD4CD25T cells to suppress EAE. This study demonstrated that in vitro activation of CD4CD8CD25 cells by MBP/rIL-2 induced relevant antigen-specific Treg within days, which expressed CD8α, CD8β and CD62L with a Ts1 phenotype and that had greater potency than freshly isolated antigen naive CD4CD25Treg in suppressing clinical severity of EAE and immune inflammation in CNS. These findings may guide development of antigen-specific Treg for therapy.

关键词： Chronic infectious disease   Direct-acting antiviral (DAA) treatment   Global Health Sector Strategy (GHSS)   HCV elimination goals   HCV treatment access   Hepatitis C (HCV)   Liver disease   Viral hepatitis elimination  

关键词： Canine   Intestinal epithelial cells   Intestinal organoids   MHC class II   IFN-gamma   Translational medicine   Comparative medicine  

摘要： BackgroundsThe interplay between intestinal epithelial cells (IECs), the immune system, and the gut microbiome is pivotal for maintaining gastrointestinal homeostasis and mediating responses to ingested antigens. IECs, capable of expressing Major Histocompatibility Complex (MHC) class II molecules, are essential in modulating immune responses, especially CD4 + T cells, in both physiological and pathological contexts. The expression of MHC class II on IECs, regulated by the class II transactivator (CIITA) and inducible by cytokine IFN-gamma, has been traditionally associated with professional antigen-presenting cells but is now recognized in the context of inflammatory conditions such as inflammatory bowel disease (IBD). In veterinary medicine, particularly among canine populations, MHC (or Dog Leukocyte Antigen, DLA) expression on IECs underlines its significance in intestinal immune pathologies, yet remains underexplored. This study aims to leverage canine intestinal organoids as a novel in vitro model to elucidate MHC class II expression dynamics and their implications in immune-mediated gastrointestinal diseases, bridging the gap between basic research and clinical application in canine *** colonoids derived from healthy dogs showed significant expression of MHC class II and its promoter gene, CIITA, after IFN-gamma treatment. This MHC class II induction was even more pronounced in differentiated colonoids cultured in Wnt-3a-depleted *** study provides insights into the role of IECs as antigen-presenting cells and demonstrates the use of intestinal organoids for investigating epithelial immune responses in inflammatory conditions.

摘要： Therapeutic drug monitoring (TDM) is increasingly valuable for tailoring personalized therapy, particularly in managing chronic inflammatory diseases where overtreatment can cause significant side effects. Monoclonal antibodies (mAbs), a primary therapeutic approach for these conditions, face challenges from antidrug antibodies (ADAs), which can reduce mAb bioavailability and efficacy. To address these issues, we utilized Tumor Necrosis Factor alpha (TNF-alpha) as a binding moiety in a fluorescence-based programmable nanosensor within the NanoHYBRID (NH) platform developed by Ulisse Biomed S.p.A. By directly conjugating TNF-alpha to DNA probes, we developed a rapid, homogeneous, affinity-based assay capable of detecting multiple mAbs targeting distinct epitopes on the same protein. This NH platform effectively detected therapeutic concentrations of clinically relevant mAbs, such as Infliximab, Adalimumab, and Golimumab, in blood serum samples in a one-step process, bypassing the need for time-intensive washing steps. Moreover, the NH sensor exhibited heightened sensitivity to the presence of ADA, which impacted drug quantification, indicating its utility for monitoring bioavailable mAb levels. Compared to ELISA, the NH platform demonstrated superior sensitivity to ADAs, suggesting its potential as a highly specific, modular solution for TDM. This modular design allows the NH platform to create multiepitope nanosensors capable of measuring bioavailable mAbs in a single step.

关键词： Cyclic voltammetry  

摘要： Methyl parathion (MP) is a widely used pesticide;it is recognized as being toxic to both target and non-target species, posing serious risks to environmental and human health. Monitoring and controlling MP residues is thus essential, necessitating the development of innovative sensors that are highly sensitive, selective, and reproducible. In the present study, an efficient electrochemical MP sensor is proposed based on silver nanoparticles (AgNPs) in conjunction with graphene oxide/ionic liquid (GO/IL) on screen printed electrodes (AgNPs@GO/IL@SPCE). The AgNPs were synthesized via a cost-effective wet-chemical process and characterized using UV-Vis spectroscopy and transmission electron microscopy (TEM). The modified electrodes were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The active surface area and charge transfer were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), respectively. The modified electrodes' electrocatalytic performance towards the reduction of MP was investigated by CV, complemented by semiempirical quantum chemistry calculations to elucidate the interaction and the electrochemical reduction mechanism of MP. The sensor demonstrates a remarkable limit of detection of 0.009 mu mol L-1 within a linear range of 0.025 to 200 mu mol L-1. It has an excellent analytical performance in terms of selectivity, reproducibility, and long-term stability over 60 days. The designed sensor was effectively used to inspect MP in groundwater and surface water samples, with recovery values ranging from 95.60% to 99.68%.

摘要： To investigate the effect of tumor necrosis factor α (TNF-α) on the permeability of blood labyrinth barrier in C57BL/6J male mice and its possible mechanism. As for the design of animal experiment, twenty male C57BL/6J mice aged 6-8 weeks were randomly divided into control group and cisplatin group with 10 mice in each group by software method. The control group was intraperitoneally injected with normal saline every day, and the cisplatin group was intraperitoneally injected with 4 mg/kg cisplatin for 4 consecutive days. After administration, auditory brainstem response (ABR) was used to detect hearing changes in mice. HE staining was used to observe the morphological changes of mouse cochlea vasculature. The expression of TNF-α was detected by immunohistochemistry and ELISA. The permeability of the blood labyrinth barrier was observed by Evans blue staining. With respect to the design of cell experiment, primarily cultured cochlea pericytes (PC) and endothelial cells (EC) were divided into EC group, EC+TNF-α group, EC+PC group, EC+PC+TNF-α group, EC+PC+TNF-α+SB-3CT (MMP-9/MMP-2 secretion inhibitor) group, PC group, PC+TNF-α group, PC+TNF-α+LY294002 (PI3K/AKT pathway inhibitor) group, PC+LY294002 group. The protein expressions of ZO-1, VE-cadherin, MMP-9, MMP-2, PI3K, p-PI3K, AKT, and p-AKT were detected by Western blot. TEER and FITC-dextran penetration experiment were used to detect EC resistance and monolayer EC permeability, respectively. The data were statistically analyzed using GraphPad Prism 8 software. In animal experiment, compared with control group, the ABR response threshold of mice in cisplatin group was increased (<0.01). The vaccine ular structure of the cochlea was disordered red, wrinkled and vacuole increased. The extravasation of vascular red fluorescent dye increased (<0.05), and also, levels of serum TNF-α and cochlear veins increased (<0.01). In cell experiment, by treatment of EC with different concentrations of cisplatin, 20 μmol cisplati

关键词： Heart Failure   Transverse aortic constricition   Interleukin-22   Inflammation   Fibrosis  

摘要： Heart failure (HF) due to left ventricular (LV) dysfunction remains a major global health challenge, with inflammation driving its progression under chronic pressure overload, such as hypertension. This study explored the role of interleukin-22 (IL-22), a cytokine associated with tissue protection, in HF induced by transverse aortic constriction (TAC). IL-22 knockout (KO) mice exhibited exacerbated HF, marked by worsened LV hypertrophy, heightened inflammation, and impaired cardiac function compared to wild-type controls. Conversely, treatment with recombinant IL-22Fc improved LV function, reduced inflammatory cell infiltration, and alleviated cardiac remodeling and inflammation. These findings demonstrate that IL-22 plays a critical role in regulating inflammation and cardiac remodeling in pressure overload-induced HF. Targeting IL-22 may represent a promising therapeutic strategy to alleviate HF progression and associated pulmonary complications.