Clinical and Experimental Immunology

Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, and brain tissue of people with relapsing remitting multiple sclerosis (RRMS) and are linked to disease progression and treatment responses. CD4+ T cells are pathogenic in RRMS, and defective T cell function could be mediated in part by liver X receptors (LXRs) - nuclear receptors that regulate lipid homeostasis and immunity. RNA-sequencing and pathway analysis identified that genes within the 'lipid metabolism' and 'signalling of nuclear receptors' pathways were dysregulated in CD4+ T cells isolated from RRMS patients compared with healthy donors...

Peri-implantitis and periodontitis are common oral inflammatory diseases, which seem to exhibit critical differences in some of their molecular features. Thus, we assessed the immune cell composition of peri-implantitis and periodontitis lesions and the corresponding inflammatory profile in soft tissues and crevicular fluid. Peri-implantitis, periodontitis and control patients were recruited (n=62), and soft tissue biopsies were collected during surgery. Crevicular fluid around implant or tooth was collected...

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, qPCR and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2 and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA...

The intestine hosts the largest immune cell compartment in the body as a result of its continuous exposure to exogenous antigens. The intestinal barrier is formed by a single layer of epithelial cells which separate immune cells from the gut lumen. Bidirectional interactions between the epithelium and the immune compartment are critical for maintaining intestinal homeostasis by limiting infection, preventing excessive immune activation, and promoting tissue repair processes. However, our understanding of epithelial-immune interactions incomplete as the complexity of in vivo models can hinder mechanistic studies, cell culture models lack the cellular heterogeneity of the intestine and when established from primary cell can be difficult to maintain...

Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is aquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titres between human cytomegalovirus seropositive and seronegative infants...

No abstract text is available yet for this article.

Immune checkpoints (ICPs) play a crucial role in regulating the immune response. In the tumor, malignant cells can hijack the immunosuppressive effects of inhibitory ICPs to promote tumor progression. Extracellular vesicles (EVs) are produced by a variety of cells and contain bioactive molecules on their surface or within their lumen. The expression of ICPs has also been detected on EVs. In vitro and in vivo studies have shown that extracellular vesicle immune checkpoints (EV ICPs) have immunomodulatory effects and are involved in tumor immunity...

Excessive formation of neutrophil extracellular traps (NETs) may lead to myositis-related interstitial lung disease (ILD). There is evidence that NETs can directly injure vascular endothelial cells and play a pathogenic role in the inflammatory exudation of ILD. However, the specific mechanism is unclear. This study aimed to investigate the specific mechanism underlying NET-induced injury to human pulmonary microvascular endothelial cells (HPMECs). HPMECs were stimulated with NETs (200 ng/ml) in vitro...

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for detection of plasma cytokines and LPS. PBMC were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies...

The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress in gastric and colorectal cancer (CRC). However, its underlying mechanism in regulating intestinal inflammation remains unclear and poorly investigated. Firstly, the characteristics of Mettl3 expression in IBD patients were examined. Afterwards we generated the mice line with IECs-specific deletion of Mettl3 verified by various experiments. We continuously recorded and compared the physiological status including survival rate etc...

Macrophage activation syndrome (MAS) is a life-threatening condition, characterized by cytopenia, multi-organ dysfunction, and coagulopathy associated with excessive activation of macrophages. In this study, we investigated that the roles of α2-antiplasmin (α2AP) in the progression of MAS using fulminant MAS mouse model induced by Toll-like receptor-9 (TLR-9) agonist (CpG) and d-galactosamine (DG). α2AP deficiency attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice...

Microglia are specialized immune cells unique to the central nervous system (CNS). Microglia have a highly plastic morphology that changes rapidly in response to injury or infection. Qualitative and quantitative measurements of ever-changing microglial morphology are considered a cornerstone of many microglia-centric research studies. The distinctive morphological variations seen in microglia are a useful marker of inflammation and severity of tissue damage. Although a wide array of damage-associated microglial morphologies has been documented, the exact functions of these distinct morphologies are not fully understood...

Hereditary angioedema (HAE) is a rare inherited disorder causing recurrent of episodes of swelling that can be potentially life threatening. Treatment of HAE can be divided into on-demand treatment for swelling, and prophylaxis. The last UK consensus on HAE was in 2014 and since then, new medications for prophylaxis have been developed, with more drugs in the pipeline. International guidelines currently recommend the use of long-term prophylaxis (LTP) as the only way of achieving disease control and normalising patient lives...

Sepsis is characterised by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility to identify integrative patterns from clinical parameters, plasma biomarkers and extensive phenotyping of blood immune cells...

No abstract text is available yet for this article.

Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance. This prospective study investigated the equilibrium between memory T cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant recipients with operational tolerance (N=8), chronic rejection (N=8), and different immunosuppressive treatment regimens (N=81)...

Chronic immune activation from persistent malaria infections can induce immunophenotypic changes associated with T cell exhaustion. However, associations between T and B cells during chronic exposure remain undefined. We analyzed peripheral blood mononuclear cells from malaria-exposed pregnant women from Papua New Guinea and Spanish malaria-naïve individuals using flow cytometry to profile T cell exhaustion markers phenotypically. T cell lineage (CD3, CD4, CD8), inhibitory (PD1, TIM3, LAG3, CTLA4, 2B4) and senescence (CD28-) markers were assessed...

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor TIGIT and activating receptor CD226 are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS...

A high percentage of patients with acute coronary syndrome develop heart failure due to the ischemic event. Regulatory T (Treg) cells are lymphocytes with suppressive capacity that control the immune response and include the conventional CD4+ CD25hi Foxp3+ cells and the CD4+ CD25var CD69+ LAP+ Foxp3- IL-10+ cells. No human follow-up studies focus on Treg cells' behavior after infarction and their possible relationship with ventricular function as a sign of post-ischemic cardiac remodeling. This study aimed to analyze, by flow cytometry, the circulating levels of CD69+ regulatory T cells and CD4+ CD25hi Foxp3+ cells, its IL-10+ production as well as their function in patients with acute myocardial infarction (AMI), and its possible relation with ventricular dysfunction...

The spleen plays a role in innate- and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human G1-induced arthritis (GIA), BALB/c mice were immunized intraperitoneally three times in 4 weeks interval with the rhG1 antigen. Mice were splenectomized on day 7 (SPE1) or day 35 (SPE2) after the initiation of immunization, and were tested for clinical severity, joint radiological- and histological changes, serum levels of inflammatory cytokines and autoantibodies, and rhG1-specific immune responses, and compared to those in control mice with spleen left intact...