scholarly journals Lysosomes in T Cell Immunity and Aging

2021 ◽  
Vol 2 ◽  
Author(s):  
Jun Jin ◽  
Huimin Zhang ◽  
Cornelia M. Weyand ◽  
Jorg J. Goronzy
Keyword(s):  
T Cell ◽  
Adaptive Immunity ◽  
Metabolic Regulation ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Cell Aging ◽  
Cell Immunity ◽  
T Cell Immune Responses ◽  
T Cell Immunology

Lysosomes were initially recognized as degradation centers that regulate digestion and recycling of cellular waste. More recent studies document that the lysosome is an important signaling hub that regulates cell metabolism. Our knowledge of the role of lysosomes in immunity is mostly derived from innate immune cells, especially lysosomal degradation-specialized cells such as macrophages and dendritic cells. Their function in adaptive immunity is less understood. However, with the recent emphasis on metabolic regulation of T cell differentiation, lysosomes are entering center stage in T cell immunology. In this review, we will focus on the role of lysosomes in adaptive immunity and discuss recent findings on lysosomal regulation of T cell immune responses and lysosomal dysfunction in T cell aging.

scholarly journals Decoding the role of CBLB for innate immune responses regulating systemic dissemination during Non-Tuberculous Mycobacteria infection

2020 ◽  
Author(s):  
Srinivasu Mudalagiriyappa ◽  
Jaishree Sharma ◽  
Hazem F. M. Abdelaal ◽  
Thomas C. Kelly ◽  
Woosuk Choi ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Granulomatous Inflammation ◽  
Innate Immune ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Inflammatory Monocytes ◽  
Cell Immunity

AbstractNon-Tuberculous Mycobacteria (NTM) are ubiquitous in nature, present in soil and water, and cause primary leading to disseminated infections in immunocompromised individuals. NTM infections are surging in recent years due to an increase in an immune-suppressed population, medical interventions, and patients with underlying lung diseases. Host regulators of innate immune responses, frontiers for controlling infections and dissemination, are poorly defined during NTM infections. Here, we describe the role of CBLB, an E3-ubiquitin ligase, for innate immune responses and disease progression in a mouse model of NTM infection under compromised T-cell immunity. We found that CBLB thwarted NTM growth and dissemination in a time- and infection route- dependent manner. Mechanistically, we uncovered defects in many innate immune cells in the absence of Cblb, including poor responses of NK cells, inflammatory monocytes, and conventional dendritic cells. Strikingly, Cblb-deficient macrophages were competent to control NTM growth in vitro. Histopathology suggested the lack of early formation of granulomatous inflammation in the absence of CBLB. Collectively, CBLB is essential to mount productive innate immune responses and help prevent the dissemination during an NTM infection under T-cell deficiency.

scholarly journals Inflammasomes in pancreatic physiology and disease

2015 ◽  
Vol 308 (8) ◽  
pp. G643-G651 ◽  
Author(s):  
Rafaz Hoque ◽  
Wajahat Z. Mehal
Keyword(s):  
Metabolic Regulation ◽  
Recent Progress ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Cell Specificity ◽  
Immune Mediated ◽  
New Findings ◽  
Inflammasome Component

In this review we summarize the role of inflammasomes in pancreatic physiology and disease with a focus on acute pancreatitis where much recent progress has been made. New findings have identified inducers of and cell specificity of inflammasome component expression in the pancreas, the contribution of inflammasome-regulated effectors to pancreatitis, and metabolic regulation of inflammasome activation, which are strong determinants of injury in pancreatitis. New areas of pancreatic biology will be highlighted in the context of our evolving understanding of gut microbiome- and injury-induced inflammasome priming, pyroptosis, and innate immune-mediated regulation of cell metabolism.

scholarly journals On the Role of Melanoma-Specific CD8+ T-Cell Immunity in Disease Progression of Advanced-Stage Melanoma Patients

2004 ◽  
Vol 10 (14) ◽  
pp. 4754-4760 ◽  
Author(s):  
Monique van Oijen ◽  
Adriaan Bins ◽  
Sjoerd Elias ◽  
Johan Sein ◽  
Pauline Weder ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Advanced Stage ◽  
Cell Immunity ◽  
Melanoma Patients

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Deficiency of C3a receptor attenuates the development of diabetic nephropathy

2019 ◽  
Vol 7 (1) ◽  
pp. e000817 ◽  
Author(s):  
Xiao-Qian Li ◽  
Dong-Yuan Chang ◽  
Min Chen ◽  
Ming-Hui Zhao
Keyword(s):  
Diabetic Nephropathy ◽  
T Cell ◽  
Adaptive Immunity ◽  
Renal Damage ◽  
Inflammatory Responses ◽  
Gene Knockout ◽  
Diabetic Mice ◽  
Pathogenic Role

ObjectiveDiabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN.Research design and methodsThe expression of C3aR was examined in the renal specimen of patients with DN. Using a C3aR gene knockout mice (C3aR−/−), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a.ResultsCompared with normal controls, the renal expression of C3aR was significantly increased in patients with DN. C3aR−/− diabetic mice developed less severe diabetic renal damage compared with wild-type (WT) diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T-cell adaptive immunity in C3aR−/− diabetic mice compared with WT diabetic mice, and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophage infiltration. In vitro study demonstrated C3a can enhance macrophage-secreted cytokines which could induce inflammatory responses and differentiation of T-cell lineage.ConclusionsC3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T-cell adaptive immunity, possibly by influencing macrophage-secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.

scholarly journals Mitochondrial Lon-induced mtDNA leakage contributes to PD-L1–mediated immunoescape via STING-IFN signaling and extracellular vesicles

2020 ◽  
Vol 8 (2) ◽  
pp. e001372
Author(s):  
An Ning Cheng ◽  
Li-Chun Cheng ◽  
Cheng-Liang Kuo ◽  
Yu Kang Lo ◽  
Han-Yu Chou ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Protein Quality ◽  
Innate Immune ◽  
Oxygen Species ◽  
Diagnostic Biomarker ◽  
Cell Immunity ◽  
Insight Into ◽  
Anti Inflammation

BackgroundMitochondrial Lon is a chaperone and DNA-binding protein that functions in protein quality control and stress response pathways. The level of Lon regulates mitochondrial DNA (mtDNA) metabolism and the production of mitochondrial reactive oxygen species (ROS). However, there is little information in detail on how mitochondrial Lon regulates ROS-dependent cancer immunoescape through mtDNA metabolism in the tumor microenvironment (TME).MethodsWe explored the understanding of the intricate interplay between mitochondria and the innate immune response in the inflammatory TME.ResultsWe found that oxidized mtDNA is released into the cytosol when Lon is overexpressed and then it induces interferon (IFN) signaling via cGAS-STING-TBK1, which upregulates PD-L1 and IDO-1 expression to inhibit T-cell activation. Unexpectedly, upregulation of Lon also induces the secretion of extracellular vehicles (EVs), which carry mtDNA and PD-L1. Lon-induced EVs further induce the production of IFN and IL-6 from macrophages, which attenuates T-cell immunity in the TME.ConclusionsThe levels of mtDNA and PD-L1 in EVs in patients with oral cancer function as a potential diagnostic biomarker for anti-PD-L1 immunotherapy. Our studies provide an insight into the immunosuppression on mitochondrial stress and suggest a therapeutic synergy between anti-inflammation therapy and immunotherapy in cancer.

scholarly journals The adaptive immune role of metallothioneins in the pathogenesis of diabetic cardiomyopathy: good or bad

2019 ◽  
Vol 317 (2) ◽  
pp. H264-H275 ◽  
Author(s):  
Tingwen Ge ◽  
Youxi Yu ◽  
Jiuwei Cui ◽  
Lu Cai
Keyword(s):  
T Cell ◽  
Adaptive Immunity ◽  
T Cell Activation ◽  
Diabetic Cardiomyopathy ◽  
Immune Cell ◽  
Antioxidant Properties ◽  
Zinc Homeostasis ◽  
Diabetic Patients ◽  
Low Grade

Diabetes is a metabolic disorder characterized by hyperglycemia, resulting in low-grade systemic inflammation. Diabetic cardiomyopathy (DCM) is a common complication among diabetic patients, and the mechanism underlying its induction of cardiac remodeling and dysfunction remains unclear. Numerous experimental and clinical studies have suggested that adaptive immunity, especially T lymphocyte-mediated immunity, plays a potentially important role in the pathogenesis of diabetes and DCM. Metallothioneins (MTs), cysteine-rich, metal-binding proteins, have antioxidant properties. Some potential mechanisms underlying the cardioprotective effects of MTs include the role of MTs in calcium regulation, zinc homeostasis, insulin sensitization, and antioxidant activity. Moreover, metal homeostasis, especially MT-regulated zinc homeostasis, is essential for immune function. This review discusses aberrant immune regulation in diabetic heart disease with respect to endothelial insulin resistance and the effects of hyperglycemia and hyperlipidemia on tissues and the different effects of intracellular and extracellular MTs on adaptive immunity. This review shows that intracellular MTs are involved in naïve T-cell activation and reduce regulatory T-cell (Treg) polarization, whereas extracellular MTs promote proliferation and survival in naïve T cells and Treg polarization but inhibit their activation, thus revealing potential therapeutic strategies targeting the regulation of immune cell function by MTs.

Role of T cell immunity in hepatitis C virus infections

2013 ◽  
Vol 3 (4) ◽  
pp. 461-467 ◽  
Author(s):  
Mark AA Claassen ◽  
Harry LA Janssen ◽  
André Boonstra
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Immunity ◽  
Virus Infections ◽  
Cell Immunity
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