p16High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy DOI

Francisco Triana-Martinez,

Alessandra Pierantoni,

Daisy Graça

et al.

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

Published: July 15, 2024

The ability of an organism to overcome infectious diseases has traditionally been linked killing invading pathogens. Accumulating evidence, however, indicates that, apart from restricting pathogen loads, organismal survival is coupled additional yet poorly understood mechanism called disease tolerance. Here we report that p16 High immune cells play a key role in establishing We found the FDA-approved BNT162b2 mRNA COVID-19 vaccine potent and rapid inducer subsets both mice humans. In turn, were indispensable for counteracting different lethal conditions, including LPS-induced sepsis, acute SARS-CoV-2 infection ionizing irradiation. Mechanistically, propose activation TLR7 or low physiological activity STING sufficient induce subset establishes adenosine environment Furthermore, containing these signals within beneficial range by deleting MDA5 appeared maintain STING, induces delays organ deterioration upon aging with improved healthspan. Our data highlight

Language: Английский

Understanding nucleic acid sensing and its therapeutic applications DOI Creative Commons

Ling-Zu Kong,

Seok‐min Kim, Chunli Wang

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(11), P. 2320 - 2331

Published: Nov. 9, 2023

Abstract Nucleic acid sensing is involved in viral infections, immune response-related diseases, and therapeutics. Based on the composition of nucleic acids, sensors are defined as DNA or RNA sensors. Pathogen-associated acids recognized by membrane-bound intracellular receptors, known pattern recognition receptors (PRRs), which induce innate immune-mediated antiviral responses. PRR activation tightly regulated to eliminate infections prevent abnormal excessive an essential mechanism tumor immunotherapy gene therapies that target cancer infectious diseases through genetically engineered cells therapeutic acids. supports priming desirable responses during treatment. Recent studies have shown affects efficiency therapy inhibiting translation. Suppression immunity induced small-molecule inhibitors, virus-derived proteins, chemical modifications offers a potential strategy. Herein, we review mechanisms regulation sensing, specifically covering recent advances. Furthermore, summarize discuss research progress regarding different effects efficacy. This study provides insights for application therapy.

Language: Английский

Citations

29
Innate virus-sensing pathways in B cell systemic autoimmunity DOI
Carola G. Vinuesa, Amalie Grenov, George Kassiotis

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6644), P. 478 - 484

Published: May 4, 2023

Although all multicellular organisms have germ line-encoded innate receptors to sense pathogen-associated molecular patterns, vertebrates also evolved adaptive immunity based on somatically generated antigen B and T cells. Because randomly may react with self-antigens, tolerance checkpoints operate limit but not completely prevent autoimmunity. These two systems are intricately linked, playing an instrumental role in the induction of antiviral immunity. In this work, we review how inborn errors can instigate cell Increased nucleic acid sensing, often resulting from defects metabolizing pathways or retroelement control, break converge into TLR7-, cGAS-STING-, MAVS-dominant signaling pathways. The syndromes span a spectrum that ranges chilblain systemic lupus severe interferonopathies.

Language: Английский

Citations

26
IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities DOI Creative Commons

He Xu,

Abdalla M. Wedn, Jian Wang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107063 - 107063

Published: Jan. 11, 2024

Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating signaling pathways to defend the host. Recent studies have revealed additional regulatory functions STING beyond its immune-related activities, including regulation cellular metabolism, DNA repair, senescence, autophagy various cell deaths. These findings highlight broader implications in physiology role immunity. Currently, approximately 10 agonists entered clinical stage. Unlike inhibitors, which maximum inhibition limit, potential infinite amplification. complex process that requires precise ensure balanced responses prevent detrimental autoinflammation. research on structural mechanism autoinhibition negative by adaptor protein 1 (AP-1) provides valuable insights into different effects under physiological pathological conditions, offering new perspective developing drugs. Herein, we present comprehensive overview molecular mechanisms regulation, along with updated details mechanisms. We discuss these regulations diseases, emphasizing importance feasibility targeting immunity-dependent or immunity-independent STING. Moreover, current trend drug development key points research, basic translational related

Language: Английский

Citations

14
Aicardi–Goutières syndrome: A monogenic type I interferonopathy DOI Open Access

Anran Liu,

Songcheng Ying

Scandinavian Journal of Immunology, Journal Year: 2023, Volume and Issue: 98(4)

Published: July 29, 2023

Aicardi-Goutières syndrome (AGS) is a rare monogenic autoimmune disease that primarily affects the brains of children patients. Its main clinical features include encephalatrophy, basal ganglia calcification, leukoencephalopathy, lymphocytosis and increased interferon-α (IFN-α) levels in patient's cerebrospinal fluid (CSF) serum. AGS may be caused by mutations any one nine genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1, LSM11 RNU7-1) result accumulation self-nucleic acids cytoplasm or aberrant sensing acids. This triggers overproduction type I interferons (IFNs) subsequently causes AGS, prototype interferonopathies. review describes discovery history with various genotypes provides latest knowledge manifestations causative AGS. The relationship between interferonopathy potential therapeutic methods for are also discussed this review.

Language: Английский

Citations

22
Nucleic acid triggers of autoimmunity and autoinflammation DOI Creative Commons
Kaiyuan Hao, Ann Marshak‐Rothstein

Current Opinion in Immunology, Journal Year: 2025, Volume and Issue: 93, P. 102535 - 102535

Published: Jan. 30, 2025

Language: Английский

Citations

0
EFTUD2 is a promising diagnostic and prognostic indicator involved in the tumor immune microenvironment and glycolysis of lung adenocarcinoma DOI Creative Commons
Ankang Yin,

Yufan Xu,

Xiyang Su

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 1, 2025

Elongation Factor Tu GTP Binding Domain Containing 2 (EFTUD2), a conserved spliceosomal GTPase, is involved in craniofacial development and various cancers, but its role lung adenocarcinoma (LUAD) remains unclear. EFTUD2 expression LUAD tissues was analyzed using data from TCGA GEO, validated by immunohistochemistry, RT-qPCR, Western blotting. The relationship between clinical features examined Fisher's exact test. Diagnostic prognostic analyses were performed R. Hub genes related to identified through topological algorithms, immune infiltration assessed CIBERSORT. cGAS-STING pathway m6A modification also the cohort. Functional assays conducted assess EFTUD2's impact on cell proliferation, cycle, invasion, metastasis, while glycolytic enzyme levels measured upregulated cells, correlating with N classification, visceral pleural intravascular tumor embolism, cytokeratin-19 fragment antigen 21-1. Sixteen EFTUD2-related hub identified. Higher linked altered infiltration, increased TumorPurity scores decreased StromalScore, ImmuneScore, ESTIMATEScore values. Gene enrichment highlighted involvement adhesion, response. strongly associated modification. knockdown inhibited migration, tumorigenicity, causing G0/G1 phase cycle arrest, expression. These findings may suggest that positively regulates progression of modulates activity making it valuable for treatment prognosis. potential diagnostic marker LUAD, microenvironment, pathway, modification, glycolysis.

Language: Английский

Citations

0
DNA damage response defects in hematologic malignancies: mechanistic insights and therapeutic strategies DOI
Marwan Kwok, Angelo Agathanggelou, Tatjana Stanković

et al.

Blood, Journal Year: 2024, Volume and Issue: 143(21), P. 2123 - 2144

Published: March 8, 2024

Language: Английский

Citations

3
A 33-year diagnostic odyssey in an Ashkenazi Jewish patient with Aicardi–Goutières syndrome. DOI Creative Commons
Oskar Schnappauf, Hongying Wang, Ivona Aksentijevich

et al.

Journal of Allergy and Clinical Immunology Global, Journal Year: 2025, Volume and Issue: 4(2), P. 100400 - 100400

Published: Jan. 5, 2025

The critical need for awareness and genetic testing of the SAMHD1 deletion in Ashkenazi Jewish patients is highlighted owing to its relatively high carrier frequency. Early detection can prevent severe disease complications through targeted therapy.

Language: Английский

Citations

0
Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy DOI Creative Commons

Z.C. Chen,

Rayk Behrendt,

Lennart Wild

et al.

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

Published: March 19, 2025

Abstract Nucleic acids from both self- and non-self-sources act as vital danger signals that trigger immune responses. Critical illnesses such acute respiratory distress syndrome, sepsis, trauma ischemia lead to the aberrant cytosolic accumulation massive release of nucleic are detected by antiviral innate receptors in endosome or cytosol. Activation for deoxyribonucleic ribonucleic triggers inflammation, a major contributor morbidity mortality critically ill patients. In past decade, there has been growing recognition therapeutic potential targeting acid sensing critical care. This review summarizes current knowledge ischemia. Given extensive research on common pathological conditions like cancer, autoimmune disorders, metabolic disorders aging, we provide comprehensive summary beyond illness offer insights may inform its role conditions. Additionally, discuss strategies specifically target sensing. By examining sources, sensor activation function, well impact regulating these pathways across various diseases, highlight driving illness.

Language: Английский

Citations

0
An evolutionary perspective to innate antiviral immunity in animals DOI Creative Commons
João T. Marques, Carine Meignin, Jean‐Luc Imler

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114678 - 114678

Published: Aug. 27, 2024

Viruses pose a significant threat to cellular organisms.Innate antiviral immunity encompasses both RNA-and protein-based mechanisms designed sense and respond infections, fundamental aspect present in all living organisms.A potent RNA-based mechanism is RNA interference, where small RNA-programmed nucleases target viral RNAs.Protein-based often rely on the induction of transcriptional responses triggered by recognition infections through innate immune receptors.These involve upregulation genes aimed at countering infections.In this review, we delve into recent advances understanding diversification animals.An evolutionary perspective gains losses diverse animals coupled mechanistic studies model organisms such as fruit fly Drosophila melanogaster essential provide deep that can be translated new strategies treatment diseases.

Language: Английский

Citations

3