Journal of cellular immunology最新文献

Metabolic alterations induced by unhealthy lifestyles, including obesity and insulin resistance are often associated with increased innate immune response and chronic inflammation. Cholesterol has been identified as a key metabolite driving the activation of the inflammasome and the "epigenetic memory" in long-term living hematopoietic stem cells. In addition to these mechanisms, the physiological aging of short-living neutrophils is a relevant modifier of their immune competency, as while they egress from medullary niches as "fresh", fully competent, cells, they turn into "aged", disarmed cells, when they extravasate into peripheral tissues to fight against pathogens or they reach the spleen for disposal. We recently observed that cardio-metabolic alterations induced by a lipid enriched unhealthy diet critically accelerate this process. Indeed, the chronic feeding with a high fat diet (HFD) results in the increase of aged neutrophils in the circulation and their accumulation in liver. This profile is associated with a deteriorated insulin response and obesity. The HFD primes aged, but not fresh neutrophils, to infiltrate in the liver and promotes inflammation coupled to altered cell immune architecture in visceral adipose tissue. Preventing the aging of neutrophils via selective ablation of CXCR2, reduces the development of obesity and improves the sensitivity to insulin. In humans, plasma levels of CXCL1, one of the cytokines binding CXCR2 and promoting neutrophil aging, are directly associated with abdominal adiposity and fatty liver independently of other risk factors. Together these findings point to a direct role of aged neutrophils in the development of metabolic disorders.

Stroke is a debilitating neurologic condition characterized by an interruption or complete blockage of blood flow to certain areas of the brain. While the primary injury occurs at the time of the initial ischemic event or hemorrhage, secondary injury mechanisms contribute to neuroinflammation, disruption of the blood-brain barrier (BBB), excitotoxicity, and cerebral edema in the days and hours after stroke. Of these secondary mechanisms of injury, significant dysregulation of various immune populations within the body plays a crucial role in exacerbating brain damage after stroke. Pathological activity of glial cells, infiltrating leukocytes, and the adaptive immune system promote neuroinflammation, BBB damage, and neuronal death. Chronic immune activation can additionally encourage the development of neurologic deficits, immunosuppression, and dysregulation of the gut microbiome. As such, immunotherapy has emerged as a promising strategy for the clinical management of stroke in a highly patient-specific manner. These strategies include regulatory T cells (Tregs), cell adhesion molecules, cytokines, and monoclonal antibodies. However, the use of immunotherapy for stroke remains largely in the early stages, highlighting the need for continued research efforts before widespread clinical use.

Heparin is a highly sulfated, hence highly polyanionic, glycosaminoglycan with a repeating disaccharide that contains a hexuronic acid, and it has been used as an anticoagulant clinically for more than half a century. Daily IP injections of small amounts of heparin in the STZ diabetic rat prevented these pathological responses even though the animals sustained hyperglycemic levels of glucose throughout. However, the structural determinant that mediates this activity is not clear. This paper describes our finding that the responses of hyperglycemic dividing mesangial cells to heparin are mediated by its non-reducing terminal trisaccharide and proposes that the non-reducing end tri-saccharide of heparin acts as a scavenger tool to detoxify the glucose toxicity in diabetes.

Vaccines are among the most effective tools for combatting the impact and spread of infectious diseases. However, the effectiveness of a vaccine can be diminished by vaccine inequality, particularly during severe outbreaks of infectious diseases in resource-poor areas. As seen in many developing countries that lack adequate healthcare infrastructure and economic resources, the acquisition and distribution of potentially life-saving vaccines may be limited, leading to prolonged suffering and increased deaths. To improve vaccine equity, vaccine design must take into consideration the logistics needed to implement a successful vaccination drive, particularly among the most vulnerable populations. In the manuscript titled "Exploiting Pre-Existing CD4⁺ T Cell Help from Bacille Calmette-Guérin Vaccination to Improve Antiviral Antibody Responses" published in the Journal of Immunology, the authors designed a recombinant subunit vaccine against the Ebola virus (EBOV) glycoprotein that can harness the pre-existing T helper cells from prior BCG vaccination. As a recombinant subunit vaccine adjuvanted with alum, this approach has many features that make it well suited for the design of vaccines for developing nations, such as relative ease of production, scalability, and distribution. In addition, the high prevalence of BCG immunization and natural immunity to mycobacteria in many regions of the world endow such vaccines with features that should increase potency and efficacy among populations residing in such regions. As a result of using the helper activity of pre-existing BCG-specific Th cells to drive antibody responses, a lower vaccine dose is needed, which is a major advantage for vaccine manufacture. Furthermore, the BCG-specific Th cells also stimulate immunoglobulin class switching to IgG isotypes that have strong affinities for activating Fc-gamma receptors (FcγRs). Taken together, we propose that the design of subunit vaccines with intrastructural help from BCG-specific Th cells can improve protection against viral infection and represents a vaccine design that can be generally adapted to other emerging viral pathogens for the control and prevention of infection in many developing countries.

Abdominal Aortic Aneurysms (AAA) remain a clinically devastating disease with no effective medical treatment therapy. AAAs are characterized by immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Interleukin-1 (IL-1) has been shown to play role in AAA associated inflammation through immune cell recruitment and activation, endothelial dysfunction, production of reactive oxygen species (ROS), and regulation of transcription factors of additional inflammatory mediators. In this review, we will discuss the principles of IL-1 signaling, its role in AAA specific inflammation, and regulators of IL-1 signaling. Additionally, we will discuss the influence of genetic and pharmacological inhibitors of IL-1 on experimental AAAs. Evidence suggests that IL-1 may prove to be a potential therapeutic target in the management of AAA disease.