Ion Channels in Innate and Adaptive Immunity

Annual Review of Immunology, Год журнала: 2015, Номер 33(1), С. 291 - 353

Опубликована: Март 21, 2015

Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, zinc have important roles second messengers to regulate intracellular signaling pathways. By contrast, monovalent sodium potassium mainly membrane potential, which indirectly controls influx calcium cell signaling. Studies investigating human patients with mutations in ion transporters, analysis gene-targeted mice, or pharmacological experiments channel inhibitors revealed ionic signals lymphocyte development innate adaptive responses. We here review mechanisms underlying function lymphocytes cells discuss their development, responses, autoimmunity, well recent efforts develop for immunomodulatory therapy.

Язык: Английский

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Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Neuron, Год журнала: 2017, Номер 95(6), С. 1246 - 1265

Опубликована: Сен. 1, 2017

Язык: Английский

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Extracellular ATP and P2 purinergic signalling in the tumour microenvironment

Nature reviews. Cancer, Год журнала: 2018, Номер 18(10), С. 601 - 618

Опубликована: Июль 13, 2018

Язык: Английский

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DAMPs from Cell Death to New Life

Frontiers in Immunology, Год журнала: 2015, Номер 6

Опубликована: Авг. 18, 2015

Our body handles tissue damage by activating the immune system in response to intracellular molecules released injured tissues (Damage-Associated Molecular Patterns, DAMPs), a similar way as it detects molecular motifs conserved pathogens (pathogen-associated patterns, PAMPs). DAMPs are that have physiological role inside cell, but acquire additional functions when they outside cell: alert about danger, stimulate an inflammatory response, and finally promote regeneration process. Beside their passive release dead cells, some can be secreted or exposed living cells undergoing life-threatening stress. been linked inflammation related disorders: hence, inhibition of DAMP-mediated responses is promising strategy improve clinical management infection- injury-elicited diseases. However, important consider not only danger signals also central players repair. Indeed, studied for healing after sterile infection-associated inflammation. This review focused on two exemplary DAMPs, HMGB1 ATP, contribution both

Язык: Английский

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T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma

Clinical Cancer Research, Год журнала: 2018, Номер 24(17), С. 4175 - 4186

Опубликована: Фев. 13, 2018

Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation multiple immune checkpoints, known contributor to failures amid checkpoint blockade, strategy that has lacked success thus far GBM. This study among first examine, credential as bona fide, T cells infiltrating human murine GBM.Experimental Design: Tumor-infiltrating peripheral blood lymphocytes (TILs PBLs) were isolated from patients with Levels exhaustion-associated inhibitory receptors poststimulation levels cytokines IFNγ, TNFα, IL2 assessed flow cytometry. receptor Vβ chain expansion was also TILs PBLs. Similar analysis extended intracranial subcutaneous immunocompetent models glioma, breast, lung, melanoma cancers.Results: Our data reveal GBM elicits particularly severe signature by: (1) prominent checkpoints; (2) stereotyped transcriptional programs matching classical virus-induced exhaustion; (3) notable hyporesponsiveness tumor-specific cells. Exhaustion signatures differ predictably tumor identity, but remain stable across manipulated locations.Conclusions: Distinct cancers possess similarly distinct mechanisms for exhausting The poor TIL function observed highlight need better understand this tumor-imposed mode order formulate effective immunotherapeutic strategies targeting Clin Cancer Res; 24(17); 4175-86. ©2018 AACRSee related commentary Jackson Lim, p. 4059.

Язык: Английский

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The principles of directed cell migration

Nature Reviews Molecular Cell Biology, Год журнала: 2021, Номер 22(8), С. 529 - 547

Опубликована: Май 14, 2021

Язык: Английский

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The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome

Frontiers in Immunology, Год журнала: 2015, Номер 6

Опубликована: Дек. 17, 2015

T-helper 17 (Th17) and T-regulatory (Treg) cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect host from pathogenic microorganisms restrain excessive effector T-cell responses, respectively. Despite their differing functional properties, Th17 Tregs share similar developmental requirements. In fact, fate of antigen-naïve T-cells either or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6 all-trans retinoic acid (RA). Importantly, microbiome also provides immunostimulatory signals, which can activate innate, downstream adaptive, immune responses. Specific components gut have been implicated in production proinflammatory cytokines innate cells, such as IL-6, IL-23, IL-1β, subsequent generation expansion cells. Similarly, commensal bacteria metabolites promote that actively induce mucosal tolerance. As such, dysbiosis may not solely represent a consequence inflammation, but rather shape Treg/Th17 commitment influence susceptibility inflammatory bowel disease (IBD). this review, we discuss cell plasticity, its dynamic regulation microbiome, highlight impact on homeostasis disease.

Язык: Английский

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Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α

Nature Medicine, Год журнала: 2015, Номер 21(6), С. 638 - 646

Опубликована: Май 25, 2015

Язык: Английский

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Ion channels and transporters in lymphocyte function and immunity

Nature reviews. Immunology, Год журнала: 2012, Номер 12(7), С. 532 - 547

Опубликована: Июнь 15, 2012

Язык: Английский

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Metabolic pathways in T cell activation and lineage differentiation

Seminars in Immunology, Год журнала: 2016, Номер 28(5), С. 514 - 524

Опубликована: Окт. 1, 2016

Recent advances in the field of immunometabolism support concept that fundamental processes T cell biology, such as TCR-mediated activation and helper lineage differentiation, are closely linked to changes cellular metabolic programs. Although major task intermediate metabolism is provide with a constant supply energy molecular precursors for production biomolecules, dynamic regulation pathways also plays an active role shaping responses. Key glycolysis, fatty acid mitochondrial now recognized crucial players their modulation can differentially affect development lineages. In this review, we describe diverse cells engage during life cycle from naïve towards effector memory cells. We consider particular how may actively function different states. Moreover, discuss regulators mTOR or AMPK link environmental adaptations elucidate consequences on differentiation function.

Язык: Английский

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