Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(3), P. 299 - 302

Published: Feb. 21, 2022

Language: Английский

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PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens

Nature, Journal Year: 2023, Volume and Issue: 619(7968), P. 151 - 159

Published: June 21, 2023

Language: Английский

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Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Language: Английский

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Superb Silk Hydrogels with High Adaptability, Bioactivity, and Versatility Enabled by Photo-Cross-Linking

ACS Nano, Journal Year: 2024, Volume and Issue: 18(23), P. 15312 - 15325

Published: May 29, 2024

The exceptional biocompatibility and adaptability of hydrogels have garnered significant interest in the biomedical field for fabrication devices. However, conventional synthetic still exhibit relatively weak fragile properties. Drawing inspiration from photosynthesis process, we developed a facile approach to achieve harmonious combination superior mechanical properties efficient preparation silk fibroin hydrogel through photo-cross-linking technology, accomplished within 60 s. utilization riboflavin H2O2 enabled sustainable cyclic reaction, facilitating transformation tyrosine dityrosine ultimately contributing formation highly cross-linked hydrogels. These exhibited excellent elasticity restorability even after undergoing 1000 cycles compression. Importantly, our findings presented that hydrogel-encapsulated adipose stem cells possess ability stimulate cell proliferation along with stemness. This was evidenced by continuous high expression levels OCT4 SOX2 over 21 days. Additionally, can be extended various material molding platforms, including microneedles, microcarriers, bone screws. Consequently, this study offered fabricating capable real-time delivery, thereby introducing an innovative avenue designing devices machinability applications.

Language: Английский

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TNF-α signals through ITK-Akt-mTOR to drive CD4 ⁺ T cell metabolic reprogramming, which is dysregulated in rheumatoid arthritis

Science Signaling, Journal Year: 2024, Volume and Issue: 17(833)

Published: April 23, 2024

Upon activation, T cells undergo metabolic reprogramming to meet the bioenergetic demands of clonal expansion and effector function. Because dysregulated cell cytokine production phenotypes coexist in chronic inflammatory disease, including rheumatoid arthritis (RA), we investigated whether cytokines released by differentiating amplified their changes. We found that tumor necrosis factor–α (TNF-α) human naïve CD4 + upon activation stimulated expression a transcriptome increased glycolysis, amino acid uptake, mitochondrial oxidation glutamine, biogenesis. The effects TNF-α were mediated Akt-mTOR signaling kinase ITK did not require NF-κB pathway. differentiation into proinflammatory helper 1 (T H 1) 17 cells, but regulatory cells. from patients with RA showed consequent Akt phosphorylation activation. These also exhibited mass, particularly within subsets implicated disease. Together, these findings suggest cell–derived drives promoting through ITK, Akt, mTOR, which is autoinflammatory

Language: Английский

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miRNA circuit modules for precise, tunable control of gene expression

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

Abstract The ability to express transgenes at specified levels is critical for understanding cellular behaviors, and applications in gene cell therapy. Transfection, viral vectors, other delivery methods produce varying protein expression levels, with limited quantitative control, while targeted knock-in stable selection are inefficient slow. Active compensation mechanisms can improve precision, but the need additional proteins or lack of tunability have prevented their widespread use. Here, we introduce a toolkit compact, synthetic miRNA-based circuit modules that provide precise, tunable control across diverse types. These circuits, termed DIMMERs (Dosage-Invariant miRNA-Mediated Expression Regulators) use multivalent miRNA regulatory interactions within an incoherent feed-forward loop architecture achieve nearly uniform over more than two orders magnitude variation underlying dosages transcription rates. They also allow coarse fine expression, portable, functioning In addition, heuristic design algorithm enables creation orthogonal variants independently multiple genes same cell. circuits allowed dramatically improved CRISPR imaging, super-resolution imaging EGFR receptors transient transfections. toolbox provided here should tunable, dosage-invariant research, therapy, biotechnology applications. One sentence description Compact enable orthogonal, generalizable research biotechnology.

Language: Английский

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The type I IFN-IL-27 axis promotes mRNA vaccine-induced CD8⁺T cell responses

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

The ability of lipid nanoparticle (LNP)-delivered mRNA vaccines to induce type I IFNs is critical promote CD8 + T cell responses. studies presented here indicate that immunization with nucleoside modified mRNA-LNP drives myeloid expression the cytokine IL-27, which acts on antigen-specific cells sustain expansion. In vitro and in vivo revealed IFN signaling necessary for mRNA-LNP-induced IL-27 production, failed KO mice, IFNAR1-deficient mice particles also encode restored addition, mRNA-LNPs served as an adjuvant improved cytolytic responses therapeutic efficacy drive anti-pathogen anti-tumor immunity. These highlight central role induced this augment functionality response prophylactic or immunization.

Language: Английский

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The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8 ⁺ T cells

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(10)

Published: March 3, 2025

Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction cancer, requiring a substantial amount proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role transcriptional regulation this process, paired transcriptomic proteomic analyses reveal that RNA profile poorly correlated with protein levels. This discrepancy underscores importance post-translational modifications (PTMs) controlling abundance during activation. However, impact PTMs on cell dynamic remains underexplored. We identify neddylation, recently discovered PTM, activated response to receptor (TCR) stimulation enriched from colon cancer patients. Mechanistically, we found rate-limiting enzyme neural precursor expressed developmentally down-regulated 8 activating E1 (NAE1), induced by NFATc1, critical transcription factor downstream TCR signaling. Our observation revealed genetic ablation NAE1 significantly disturbed landscape related mitochondrial As result, lacking exhibited severely compromised activation, survival, which was accompanied impaired Consistently, deletion abolished their antitumor function promoted tumor progression. By contrast, overexpression improved tumor-infiltrating cells. Overall, uncovered previously underappreciated as checkpoint Enforced expression offers promising therapeutic potential boosting responses.

Language: Английский

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NK cell-derived IFNγ mobilizes free fatty acids from adipose tissue to promote early B cell activation during viral infection

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

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Specialized Ribosomes in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6334 - 6334

Published: March 28, 2023

Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or changes ribosome that regulate translation a group transcripts. These alterations have been shown affect affinity ribosomes for certain mRNAs change cotranslational folding nascent polypeptides exit tunnel. The identification requires incorporation ribosomal proteins modifications rRNA and/or protein lead(s) physiologically relevant translation. In this review, we summarize specialization mammals discuss their relevance several human diseases.

Language: Английский

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