CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate

The Journal of Experimental Medicine, Год журнала: 2022, Номер 219(6)

Опубликована: Апрель 19, 2022

CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both signaling responding to DAMPs PAMPs, well long chain free fatty acid transporter. Recent studies have indicated that can integrate metabolic pathways through its dual thereby influence differentiation activation, ultimately help determine fate. Its expression along with innate adaptive cells contribute pathogenesis of common diseases, including atherosclerosis tumor progression, which makes downstream effectors potential therapeutic targets. This review comprehensively examines the variety cells, especially macrophages T We also briefly discuss function such adipocytes platelets, impact system via intercellular communication. Finally, outstanding questions this field are provided for directions future studies.

Язык: Английский

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CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Ноя. 30, 2020

CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or receptor adhesive functions. be found expressed either on the cell surface, where it may face extracellular milieu cytosol, in compartments, such endoplasmic reticulum, nuclear membrane, mitochondria. The main expression of observed hematopoietic cells, some cell-type specific differences between mouse human. role immune cells ranges from modulating differentiation to effector functions during inflammation, regulate recruitment, cytokine release, NAD availability. In line appears also play critical inflammatory processes autoimmunity, although whether has pathogenic regulatory effects varies depending disease, cell, animal model analyzed. Given complexity physiology been difficult completely understand biology this autoimmune inflammation. review, we analyze current knowledge controversies regarding inflammation autoimmunity novel molecular tools clarify gaps field.

Язык: Английский

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Aging and the Immune System: the Impact of Immunosenescence on Viral Infection, Immunity and Vaccine Immunogenicity

Immune Network, Год журнала: 2019, Номер 19(6)

Опубликована: Янв. 1, 2019

Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components both innate and adaptive systems experience aging-related changes, such as alterations in number circulating monocytic dendritic cells, reduced phagocytic activities neutrophils, limited diversity B/T cell repertoire, T exhaustion or inflation, chronic production inflammatory cytokines known inflammaging. The elderly are less likely to benefit from vaccinations preventative measures against infectious diseases due inability mount successful defense. Therefore, aging thought decrease efficacy effectiveness vaccines, suggesting aging-associated decline immunogenicity induced vaccination. In this review, we discuss changes immunity impact immunosenescence on viral infection immunity. We further explore recent advances strategies enhance vaccines elderly. Better understanding molecular mechanisms underlying immunosenescence-related dysfunction will provide crucial insight into development effective elderly-targeted immunotherapies.

Язык: Английский

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Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

OncoImmunology, Год журнала: 2020, Номер 9(1)

Опубликована: Янв. 1, 2020

The term ‘immunogenic cell death’ (ICD) denotes an immunologically unique type of regulated death that enables, rather than suppresses, T cell-driven immune responses are specific for antigens derived from the dying cells. ability ICD to elicit adaptive immunity heavily relies on immunogenicity cells, implying such cells must encode and present not covered by central tolerance (antigenicity), deliver immunostimulatory molecules as damage-associated molecular patterns cytokines (adjuvanticity). Moreover, host system be equipped detect antigenicity adjuvanticity As cancer (but normal) express several tolerance, they can driven into some therapeutic agents, including limited to) chemotherapeutics anthracycline family, oxaliplatin bortezomib, well radiation therapy. In this Trial Watch, we describe current trends in preclinical clinical development ICD-eliciting chemotherapy partner immunotherapy, with a focus trials assessing efficacy context immunomonitoring.

Язык: Английский

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Macrophages at the interface of the co-evolving cancer ecosystem

Cell, Год журнала: 2023, Номер 186(8), С. 1627 - 1651

Опубликована: Март 15, 2023

Язык: Английский

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Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Май 11, 2023

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up 27% patients with MDD associated more severe, chronic, treatment-resistant trajectory. Inflammation not unique depression has transdiagnostic effects suggesting shared underlying psychopathologies metabolic disorders. Research supports association but necessarily causation Putative mechanisms link dysregulation the HPA axis immune cell glucocorticoid resistance resulting in hyperactivation peripheral system. The extracellular release DAMPs DAMP-PRR signaling creates feed forward loop that accelerates central inflammation. Higher plasma levels inflammatory cytokines, most consistently interleukin IL-1β, IL-6, TNF-α, are correlated greater depressive symptomatology. Cytokines sensitize axis, disrupt negative feedback loop, further propagate reactions. Peripheral inflammation exacerbates (neuroinflammation) through several including disruption blood-brain barrier, cellular trafficking, activation glial cells. Activated cells chemokines, reactive oxygen nitrogen species into extra-synaptic space dysregulating neurotransmitter systems, imbalancing excitatory inhibitory ratio, disrupting neural circuitry plasticity adaptation. particular, microglial toxicity plays role pathophysiology neuroinflammation. Magnetic resonance imaging (MRI) studies show reduced hippocampal volumes. Neural dysfunction such as hypoactivation between ventral striatum ventromedial prefrontal cortex underlies melancholic phenotype Chronic administration monoamine-based antidepressants counters response, delayed therapeutic onset. Therapeutics targeting mediated immunity, generalized specific pathways, nitro-oxidative have enormous potential advance treatment landscape. Future clinical trials will need include system perturbations biomarker outcome measures facilitate novel antidepressant development. this overview, we explore correlates elucidate pathomechanisms development biomarkers therapeutics.

Язык: Английский

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Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions

Neuron, Год журнала: 2020, Номер 109(2), С. 222 - 240

Опубликована: Дек. 2, 2020

Язык: Английский

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Mechanisms Regulating Muscle Regeneration: Insights into the Interrelated and Time-Dependent Phases of Tissue Healing

Cells, Год журнала: 2020, Номер 9(5), С. 1297 - 1297

Опубликована: Май 22, 2020

Despite a massive body of knowledge which has been produced related to the mechanisms guiding muscle regeneration, great interest still moves scientific community toward study different aspects skeletal homeostasis, plasticity, and regeneration. Indeed, lack effective therapies for several physiopathologic conditions suggests that comprehensive cellular behavior molecular pathways, regulating each regenerative stage, be devised. Hence, it is important perform even more focused studies, taking advantage robust markers, reliable techniques, reproducible protocols. Here, we provide an overview about general regeneration discuss approaches interrelated time-dependent phases healing.

Язык: Английский

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Extracellular CIRP (eCIRP) and inflammation

Journal of Leukocyte Biology, Год журнала: 2019, Номер 106(1), С. 133 - 146

Опубликована: Янв. 15, 2019

Cold-inducible RNA-binding protein (CIRP) was discovered 2 decades ago while studying the mechanism of cold stress adaptation in mammals. Since then, role intracellular CIRP (iCIRP) as a stress-response has been extensively studied. Recently, extracellular (eCIRP) to also have an important role, acting damage-associated molecular pattern, raising critical implications for pathobiology inflammatory diseases. During hemorrhagic shock and sepsis, inflammation triggers translocation from nucleus cytosol its release space. eCIRP then induces responses macrophages, neutrophils, lymphocytes, dendritic cells. endoplasmic reticulum pyroptosis endothelial cells by activating NF-κB inflammasome pathways, necroptosis macrophages via mitochondrial DNA damage. works through TLR4-MD2 receptors. Studies with

Язык: Английский

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Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection

Anesthesia & Analgesia, Год журнала: 2020, Номер 131(6), С. 1693 - 1707

Опубликована: Ноя. 13, 2020

The immune system is an evolutionary hallmark of higher organisms that defends the host against invading pathogens and exogenous infections. This defense includes recruitment cells to site infection initiation inflammatory response contain eliminate pathogens. However, may also be triggered by noninfectious stimuli such as major surgery, and, in case overshooting, still not comprehensively understood reaction, lead tissue destruction organ dysfunction. Unfortunately, some cases, effectively distinguish between elicited which ideally should only require a modest response, those trauma or pathogenic infection. Surgical procedures thus represent potential trigger for systemic inflammation causes secretion proinflammatory cytokines, endothelial dysfunction, glycocalyx damage, activation neutrophils, ultimately multisystem destruction. In this review, we discuss summarize currently available mechanistic knowledge on surgery-associated inflammation, demarcation toward other complications, possible therapeutic options. These options depend uncovering underlying mechanisms could include pharmacologic agents, remote ischemic preconditioning protocols, cytokine blockade clearance, optimization surgical procedures, anesthetic regimens, perioperative diagnostic assessment. Currently, large gap basic science clinically confirmed data exists due limited evidence base translational studies. We important steps understanding precise time- space-regulated processes inflammation.

Язык: Английский

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