Interferon- γ and infectious diseases: Lessons and prospects

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Infectious diseases continue to claim many lives. Prevention of morbidity and mortality from these would benefit not just new medicines vaccines but also a better understanding what constitutes protective immunity. Among the major immune signals that mobilize host defense against infection is interferon-γ (IFN-γ), protein secreted by lymphocytes. Forty years ago, IFN-γ was identified as macrophage-activating factor, and, in recent years, there has been resurgent interest biology its role human defense. Here we assess current IFN-γ, revisit designation an "interferon," weigh prospects therapeutic globally pervasive microbial pathogens.

Language: Английский

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The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease

Hepatology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

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The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis

Science Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on immunocytes guard homeostasis in healthy individuals remains limited. This study highlights heterogeneous, polyfunctional regulatory T cell (T reg ) compartment meninges. A subtype specialized controlling interferon-gamma (IFN-γ) responses another dedicated regulating follicular B were substantial components this compartment. Accordingly, punctual ablation rapidly unleashed IFN-γ production by lymphocytes, unlocked access parenchyma, altered profiles. Distally, hippocampus assumed a reactive state, with morphological transcriptional changes multiple glial types. Within dentate gyrus, neural stem underwent more death blocked from further differentiation, which coincided impairments short-term spatial-reference memory. Thus, regs multifaceted safeguard at steady state.

Language: Английский

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IFNγ causes mitochondrial dysfunction and oxidative stress in myositis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 26, 2024

Abstract Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of interferon γ (IFNγ) using NOD female mice deficient in inducible T cell co-stimulator ( Icos ), which have previously been shown to develop spontaneous IFNγ-driven myositis mimicking human disease. Using muscle proteomic spatial transcriptomic analyses reveal profound myofiber metabolic dysregulation these mice. In addition, report mitochondrial abnormalities oxidative stress diseased Supporting a pathogenic for stress, treatment reactive oxygen species (ROS) buffer compound alleviated myositis, preserved ultrastructure respiration, reduced inflammation. Mitochondrial anomalies were diminished following anti-IFNγ treatment. Further analysis IIMs patients myoblast vitro studies supported link between IFNγ dysfunction observed These results suggest that dysfunction, ROS inflammation interconnected self-maintenance loop, opening perspectives mitochondria therapy and/or targeting drugs myositis.

Language: Английский

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Immunological regulation of skeletal muscle adaptation to exercise

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(6), P. 1175 - 1183

Published: April 25, 2024

Language: Английский

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Niche-specific control of tissue function by regulatory T cells—Current challenges and perspectives for targeting metabolic disease

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(2), P. 229 - 239

Published: Jan. 12, 2024

Tissue regulatory T cells (Tregs) exert pivotal functions in both immune and metabolic regulation, maintaining local tissue homeostasis, integrity, function. Accordingly, Tregs play a crucial role controlling obesity-induced inflammation supporting efficient muscle function repair. Depending on the context, are characterized by unique transcriptomes, growth, survival factors cell receptor (TCR) repertoires. This functional specialization offers potential to selectively target context-specific Treg populations, tailoring therapeutic strategies specific niches, thereby minimizing side effects. Here, we discuss challenges perspectives for niche-specific targeting, which holds promise highly precise medical interventions combat disease.

Language: Английский

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Molecular aspects of the exercise response and training adaptation in skeletal muscle

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 53 - 68

Published: July 24, 2024

Skeletal muscle plasticity enables an enormous potential to adapt various internal and external stimuli perturbations. Most notably, changes in contractile activity evoke a massive remodeling of biochemical, metabolic force-generating properties. In recent years, large number signals, sensors, regulators effectors have been implicated these adaptive processes. Nevertheless, our understanding the molecular underpinnings training adaptation remains rudimentary. Specifically, mechanisms that underlie signal integration, output coordination, functional redundancy other complex traits are unknown. fact, it is even unclear how stimulus-dependent specification brought about endurance or resistance exercise. this review, we will provide overview on events describe acute perturbations single exercise bouts. Furthermore, insights into principles long-term adaptation. Finally, current gaps knowledge be identified, strategies for multi-omic –cellular analyses skeletal engaged individual, bouts chronic discussed.

Language: Английский

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Harnessing the biology of regulatory T cells to treat disease

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Language: Английский

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Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(3)

Published: Jan. 13, 2025

Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced exercise. A potential source of is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions exercise-induced cfDNA unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program either high-intensity tactical training (HITT) or traditional moderate-intensity (TRAD). Blood plasma was collected pre- postexercise at weeks 0 12 after 4 wk detraining upon completion. Whole-genome enzymatic methylation sequencing (EM-seq) with cell-type proportion deconvolution applied obtained from 50 samples paired concentration measurements for 90 circulating cytokines. Acute increased release neutrophils, dendritic cells (DCs), macrophages proportional intensity. Exercise reduced released in HITT participants not TRAD DCs neutrophils. For most participants, lowered mitochondrial rest, even detraining. Using analysis approach we developed, concluded that rapid ETosis, process cell death where extracellular traps, likely cfDNA, demonstrated enrichment nuclear DNA. Further, several cytokines exercise, such as IL-6, IL-10, IL-16, attenuated induction only IL-6 IL-17F. Cytokine levels associated induction, suggesting main cause cfDNA. Overall, intensity modulated cytokine responses, contributing anti-inflammatory effects regular

Language: Английский

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Gene Therapy and Diabetes: A Narrative Review of Recent Advances and the Role of Multidisciplinary Healthcare Teams

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 107 - 107

Published: Jan. 20, 2025

Introduction: Gene therapy has emerged as a promising frontier in the management of diabetes, offering innovative approaches to address both type 1 and 2 diabetes. This narrative review examines advancements gene applications, focusing on animal human studies, includes total 11 studies adherence PRISMA guidelines. These utilize various viral vectors, such adeno-associated virus (AAV) lentivirus, deliver genes that regulate insulin production enhance angiogenesis. aims synthesize recent for diabetes its complications, explore evolving role pharmacists this emerging field. Methods: A comprehensive search was conducted identify relevant Databases PubMed, Cochrane Database Systematic Reviews, Central Register Controlled Trials, Google Scholar were queried using keywords “Diabetes”, “gene therapy”, “Type diabetes”, diabetes”. Both included provide broad perspective Results: Animal model have shown results, including sustained production, improved glucose homeostasis, enhanced wound healing. Human though fewer number, reported significant advancements. Patients with diabetic neuropathy treated plasmid VEGF recombinant (rAAV) showed improvements neuropathic symptoms glycemic control. Other involving intramuscular injections VM202 bicistronic VEGF165/HGF pain reduction, healing ischemic lesions, increased Conclusions: Despite these encouraging limitations small sample sizes, short follow-up periods, necessity more extensive clinical trials persist. Diabetes is metabolic syndrome requires collaboration multidisciplinary team assist several aspects implementing successful therapy. Several healthcare providers policy makers may play crucial patient education, counseling, treatments.

Language: Английский

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