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The Journal of Experimental Medicine
Scopus
ISSN 0022-1007 · Rockefeller University Press · 39 artikel di indeks
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CAR-T cell manufacturing: Major process parameters and next-generation strategies
Chimeric antigen receptor (CAR)-T cell therapies have demonstrated strong curative potential and become a critical component in the array of B-cell malignancy treatments. Successful deployment of CAR-T cell therapies to treat hematologic and solid cancers, as well as other indications such as…
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CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate
CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both a signaling receptor responding to DAMPs and PAMPs, as well as a long chain free fatty acid transporter. Recent studies have indicated that CD36 can integrate cell signaling…
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Neutrophil phenotypes and functions in cancer: A consensus statement
Neutrophils are the first responders to infection and inflammation and are thus a critical component of innate immune defense. Understanding the behavior of neutrophils as they act within various inflammatory contexts has provided insights into their role in sterile and infectious diseases…
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Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration
Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but is also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal fluid (CSF). However, it remains elusive whether…
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Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions
Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia…
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Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice
In this study, using single-cell RNA-seq, cell mass spectrometry, flow cytometry, and functional analysis, we characterized the heterogeneity of polymorphonuclear neutrophils (PMNs) in cancer. We describe three populations of PMNs in tumor-bearing mice: classical PMNs, polymorphonuclear…
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Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Alzheimer's disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to pathology…
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Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account…
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Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection
Inflammation is an evolutionarily selected defense response to infection or tissue damage that involves activation and consumption of immune cells in order to reestablish and maintain organismal integrity. In this process, hematopoietic stem cells (HSCs) are themselves exposed to inflammatory cues…
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Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection
The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied…
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Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord
The wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting tissue damage, but eventually results in a scar-like environment that is not conducive to regeneration and repair. A better understanding of this dichotomy is critical to…
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Ferroptosis in infection, inflammation, and immunity
Ferroptosis is a type of regulated necrosis that is triggered by a combination of iron toxicity, lipid peroxidation, and plasma membrane damage. The upstream inducers of ferroptosis can be divided into two categories (biological versus chemical) and activate two major pathways (the…
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Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine
Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other…
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Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling…
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The role of IL-22 in intestinal health and disease
The cytokine interleukin-22 (IL-22) is a critical regulator of epithelial homeostasis. It has been implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs), and complement…
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Interleukin-17–induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 is involved in pancreatic tumorigenesis, but its role in invasive PDAC is undetermined. We hypothesized that IL17 triggers and sustains PDAC…
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Historical overview of the interleukin-6 family cytokine
Interleukin-6 (IL-6) has been identified as a 26-kD secreted protein that stimulates B cells to produce antibodies. Later, IL-6 was revealed to have various functions that overlap with other IL-6 family cytokines and use the common IL-6 signal transducer gp130. IL-6 stimulates cells through…
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Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells
CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the tumor microenvironment (TME) can dampen their ability to control tumor progression. We describe lipid accumulation in the TME…
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Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19
Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are thought to be major causes of respiratory failure and death, how they relate to lung…
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Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer
Experimental and clinical evidence suggests that tumor-associated macrophages (TAMs) play important roles in cancer progression. Here, we have characterized the ontogeny and function of TAM subsets in a mouse model of metastatic ovarian cancer that is representative for visceral peritoneal…