SARS-CoV-2–associated ssRNAs activate inflammation and immunity via TLR7/8

JCI Insight, Journal Year: 2021, Volume and Issue: 6(18)

Published: Aug. 10, 2021

The inflammatory and IFN pathways of innate immunity play a key role in the resistance pathogenesis coronavirus disease 2019 (COVID-19). Innate sensors SARS-CoV-2-associated molecular patterns (SAMPs) remain to be completely defined. Here, we identified single-stranded RNA (ssRNA) fragments from SARS-CoV-2 genome as direct activators endosomal TLR7/8 MyD88 pathway. same sequences induced human DC activation terms phenotype function, such cytokine production Th1 polarization. A bioinformatic scan viral several hundreds potentially activating TLR7/8, suggesting that products virus processing potently activate responses downstream these receptors. In vivo, SAMPs MyD88-dependent lung inflammation characterized by accumulation proinflammatory cytotoxic mediators immune cell infiltration, well splenic phenotypical maturation. These results crucial cellular sensor ssRNAs encoded involved host COVID-19.

Language: Английский

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Dendritic cells as orchestrators of anticancer immunity and immunotherapy

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(4), P. 257 - 277

Published: Feb. 7, 2024

Language: Английский

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Circulating tumor cell-blood cell crosstalk: Biology and clinical relevance

Cell Reports, Journal Year: 2022, Volume and Issue: 40(9), P. 111298 - 111298

Published: Aug. 1, 2022

Circulating tumor cells (CTCs) are the seeds of distant metastasis, and number CTCs detected in blood cancer patients is associated with a worse prognosis. face critical challenges for their survival circulation, such as anoikis, shearing forces, immune surveillance. Thus, understanding mechanisms interactions within microenvironment crucial better metastatic progression development novel treatment strategies. interact different hematopoietic cells, platelets, red neutrophils, macrophages, natural killer (NK) lymphocytes, endothelial cancer-associated fibroblasts, which can affect CTC blood. This interaction may take place either via direct cell-cell contact or through secreted molecules. Here, we review discuss potential clinical relevance these biomarkers targets anti-metastatic therapies.

Language: Английский

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The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 12, 2024

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.

Language: Английский

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Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses

Immunity, Journal Year: 2023, Volume and Issue: 56(6), P. 1341 - 1358.e11

Published: June 1, 2023

Type 1 conventional dendritic cells (cDC1s) are critical for anti-cancer immunity. Protective immunity is thought to require cDC1s sustain T cell responses within tumors, but it poorly understood how this function regulated and whether its subversion contributes immune evasion. Here, we show that tumor-derived prostaglandin E2 (PGE2) programmed a dysfunctional state in intratumoral cDC1s, disabling their ability locally orchestrate CD8+ responses. Mechanistically, cAMP signaling downstream of the PGE2-receptors EP2 EP4 was responsible programming cDC1 dysfunction, which depended on loss transcription factor IRF8. Blockade PGE2-EP2/EP4-cDC1 axis prevented dysfunction reinvigorated responses, achieved cancer control. In human PGE2-induced conserved associated with poor patient prognosis. Our findings reveal cDC1-dependent checkpoint targeted by PGE2

Language: Английский

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A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(8), P. 1498 - 1515.e10

Published: July 13, 2023

Type 1 conventional dendritic cells (cDC1) can support T cell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8+ clustering as a unique feature of immunity. These clusters form selectively in stromal tumor regions and constitute niches which cDC1 activate TCF1+ stem-like CD8+ cells. We distinct population immunostimulatory CCR7neg that produce CXCL9 promote cluster formation cross-present antigens these niches, required for differentiation expansion promotes cancer immune control. Similarly, human cancers, interact with are associated patient survival. Our findings reveal an phase the response orchestrated by tumor-residing could be exploited therapy.

Language: Английский

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Extricating human tumour immune alterations from tissue inflammation

Nature, Journal Year: 2022, Volume and Issue: 605(7911), P. 728 - 735

Published: May 11, 2022

Abstract Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain 1,2 . An inherent weakness current approaches is that therapeutically targeted pathways are not restricted to tumours, also found other tissue microenvironments, complicating 3,4 Despite great efforts define inflammatory processes tumour microenvironment, understanding tumour-unique immune alterations limited by a knowledge gap regarding cell populations inflamed human tissues. Here, an effort identify such tumour-enriched alterations, we used complementary single-cell analysis interrogate infiltrate head and neck squamous carcinomas site-matched non-malignant, Our revealed large overlap composition phenotype cells Computational identified interactions, one which yields population regulatory T (T reg ) highly enriched uniquely among all haematopoietically-derived blood co-expression ICOS IL-1 receptor type 1 (IL1R1). We provide evidence these intratumoural IL1R1 + had responded antigen recently demonstrate they clonally expanded with superior suppressive function compared − cells. In addition identifying extensive immunological congruence between tissues tumours as well tumour-specific changes direct disease relevance, our work provides blueprint for extricating disease-specific from general inflammation-associated patterns.

Language: Английский

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Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors

Immunity, Journal Year: 2023, Volume and Issue: 56(8), P. 1761 - 1777.e6

Published: July 27, 2023

Language: Английский

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Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches

Immunity, Journal Year: 2022, Volume and Issue: 55(4), P. 656 - 670.e8

Published: April 1, 2022

Language: Английский

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Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells

Nature, Journal Year: 2023, Volume and Issue: 620(7975), P. 881 - 889

Published: Aug. 9, 2023

Language: Английский

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