The immunology and immunopathology of COVID-19

Science, Journal Year: 2022, Volume and Issue: 375(6585), P. 1122 - 1127

Published: March 10, 2022

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify drivers of and fatal COVID-19, understand what leads prolongation symptoms after disease resolution. We review results almost years COVID-19 immunology discuss definitive findings remaining questions regarding our understanding pathophysiology. emerging differences in responses seen those with without Long Covid syndrome, also known as post-acute sequelae SARS-CoV-2. hope that knowledge gained from this will be applied studies inflammatory processes involved critical chronic illnesses, which remain a major unmet need.

Language: Английский

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A global view of the interplay between non-alcoholic fatty liver disease and diabetes

The Lancet Diabetes & Endocrinology, Journal Year: 2022, Volume and Issue: 10(4), P. 284 - 296

Published: Feb. 17, 2022

Language: Английский

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TGF-β signaling in health, disease and therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 22, 2024

Abstract Transforming growth factor (TGF)-β is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-β can stimulate diverse cellular responses particularly critical to embryonic development, wound healing, homeostasis, immune homeostasis in health. dysfunction play key roles many diseases, numerous targeted therapies have been developed rectify its pathogenic activity. In the past decades, large number studies on signaling carried out, covering broad spectrum topics health, disease, therapeutics. Thus, comprehensive overview required for general picture this field. review, we retrace research history introduce molecular mechanisms regarding biosynthesis, activation, transduction. We also provide deep insights into functions physiological conditions as well pathological processes. TGF-β-targeting which brought fresh hope treatment relevant diseases are highlighted. Through summary previous knowledge recent updates, review aims systematic understanding attract more attention interest area.

Language: Английский

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Immune response in COVID-19: what is next?

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1107 - 1122

Published: May 17, 2022

Abstract The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle quality in unprecedented ways. A better understanding of immunity its regulation response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here various virus mutations evolving manifestations along with alterations immune responses specific focuses innate response, neutrophil extracellular traps, humoral immunity, cellular immunity. Different types vaccines were compared analyzed based their unique properties elicit Various therapeutic strategies such as antibody, anti-viral medications inflammation control discussed. We predict that available continuously emerging new technologies, powerful administration schedules, effective public health measures, COVID-19 will be under near future.

Language: Английский

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SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic

Immunity, Journal Year: 2022, Volume and Issue: 55(10), P. 1764 - 1778

Published: Aug. 18, 2022

Language: Английский

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Ferroptosis: a double-edged sword mediating immune tolerance of cancer

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(11)

Published: Nov. 5, 2022

Abstract The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type necrosis distinguished from apoptosis autophagy. Actuated by phospholipid peroxidation, modulated various cellular metabolic signaling pathways, including amino acid, lipid, iron, mitochondrial metabolism. Notably, associated with numerous diseases plays double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive ferroptosis. Hence, inducing prohibiting vastly promising potential treating drug-resistant cancers. Immunotolerant cancer not traditional death pathway such as necroptosis, while crucial role mediating immune antagonize tolerance, broad prospects clinical setting. Herein, we summarized mechanisms delineated regulatory network ferroptosis, emphasized its dual proposed significant benefits microenvironment, ultimately presented some provocative doubts. This review aims provide practical guidelines research directions for practice immune-resistant tumors.

Language: Английский

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UNC93B1 variants underlie TLR7-dependent autoimmunity

Science Immunology, Journal Year: 2024, Volume and Issue: 9(92)

Published: Jan. 11, 2024

UNC93B1 is critical for trafficking and function of nucleic acid-sensing Toll-like receptors (TLRs) TLR3, TLR7, TLR8, TLR9, which are essential antiviral immunity. Overactive TLR7 signaling induced by recognition self-nucleic acids has been implicated in systemic lupus erythematosus (SLE). Here, we report variants (E92G R336L) four patients with early-onset SLE. Patient cells or mouse macrophages carrying the produced high amounts TNF-α IL-6 upon stimulation TLR7/TLR8 agonist, but not TLR3 TLR9 agonists. E92G causes protein instability reduced interaction leading to selective hyperactivation constitutive type I IFN signaling. Thus, regulates TLR subtype-specific mechanisms ligand recognition. Our findings establish a pivotal role TLR7-dependent autoimmunity highlight therapeutic potential targeting

Language: Английский

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Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 409 - 420

Published: Feb. 16, 2024

Language: Английский

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Engineered brain‐targeting exosome for reprogramming immunosuppressive microenvironment of glioblastoma

Exploration, Journal Year: 2024, Volume and Issue: unknown

Published: June 26, 2024

Abstract The immunosuppressive microenvironment of glioblastoma multiforme (GBM) severely impacts the response to various treatments, including systemic chemotherapy. Targeted reprogramming GBM using RNA interference (RNAi) is largely restricted by poor brain delivery efficiency and targeting specificity. Herein, an acid‐cleavable transferrin (Tf) decorated engineering exosome‐based brain‐targeting system (ACTE) was proposed efficiently deliver small towards transform growth factor‐β (siTGF‐β) doxorubicin (DOX) site for combination chemo‐immunotherapy. siTGF‐β DOX co‐loaded ACTE, termed as DOX&siTGF‐β@ACTE (Ds@ACTE), designed specifically recognize Tf receptor (TfR) on blood‐brain barrier (BBB). Subsequently, Ds@ACTE undergoes acid‐responsive detachment within lysosome capillary endothelial cells, leading separation DOX&siTGF‐β@Exo (Ds@Exo) from Tf‐TfR complex enhanced BBB transcytosis. After crossing BBB, separated Ds@Exo can further target cells via homing effect. In vivo studies validated that significantly downregulated TGF‐β expression reprogram microenvironment, thereby reinforce chemotherapeutic effect DOX‐induced anti‐tumor immune response. effectiveness this strategy not only provide thinking designing a more intelligent based engineered exosomes but also explore effective treatment regimen GBM.

Language: Английский

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Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(8)

Published: March 14, 2024

SARS-CoV-2 infection of the upper airway and subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying human biopsies vitro a hamster model vivo, we demonstrated transition nasal tropism from olfactory to respiratory epithelium as virus evolved. Analyzing each variant revealed that WA1 or Delta infect proportion neurons addition primary target sustentacular cells. The possessed broader cellular invasion capacity into submucosa, while Omicron displayed enhanced longer retention sinonasal epithelium. neuronal by bulb transport via axon were more pronounced younger hosts. In addition, observed viral clearance delay phagocytic dysfunction aged mucosa accompanied decline phagocytosis related genes. Furthermore, robust basal stem cell activation contributed neuroepithelial regeneration restores ACE2 expression post-infection. Together, our study characterized strains, clearance, post infection. shifting characteristics at portal provides insight variability clinical features, particularly long COVID, may suggest differing strategies for early local intervention.

Language: Английский

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