Genome-wide association analysis of plasma lipidome identifies 495 genetic associations

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 31, 2023

The human plasma lipidome captures risk for cardiometabolic diseases. To discover new lipid-associated variants and understand the link between lipid species disorders, we perform univariate multivariate genome-wide analyses of 179 in 7174 Finnish individuals. We fine-map associated loci, prioritize genes, examine their disease links 377,277 FinnGen participants. identify 495 genome-trait associations 56 genetic loci including 8 novel with a considerable boost provided by analysis. For 26 fine-mapping identifies high causal probability, 14 coding indicating likely genes. A phenome-wide analysis across 953 endpoints reveals 40 loci. 11 coronary artery variants, detect strong species. Our study demonstrates power correlated lipidomics data diseases beyond standard lipids.

Language: Английский

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Lupus nephritis: new progress in diagnosis and treatment

Journal of Autoimmunity, Journal Year: 2022, Volume and Issue: 132, P. 102871 - 102871

Published: Aug. 20, 2022

Language: Английский

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Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

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

Published: Oct. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Language: Английский

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Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T‐ and B‐cell interactions

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

The interplay between the immune system and metabolic state of a cell is intricate. In all phases an response, corresponding changes shall occur to support its modulation, in addition signalling through cytokine environment receptor stimulation. While autoimmune disorders may develop because imbalance that modulates switching T-cell phenotypes, effects interaction T B cells have on one another's cellular metabolism are yet be understood disease context. Here, we propose perspective which highlights potential targeting modulate T- B-cell subtypes populations as well T-B B-T interactions successfully treat disorders. Specifically, envision how can tip balance interactions, definite mechanisms both health disease, explain phenotype switches cells. Within this scenario, highlight link inflammation, immunometabolism, epigenetics ageing, critical understand inflammatory combination treatments cause (T/B) imbalances, pathways involved, increase effectiveness treatment disorders, and/or ameliorate their symptoms improve patients' quality life.

Language: Английский

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Pregnancy-related complications in systemic lupus erythematosus

Journal of Autoimmunity, Journal Year: 2022, Volume and Issue: 132, P. 102864 - 102864

Published: July 21, 2022

Language: Английский

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Lipid metabolism in type 1 diabetes mellitus: Pathogenetic and therapeutic implications

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease with insulin deficiency due to pancreatic β cell destruction. Multiple independent cohort studies revealed specific lipid spectrum alterations prior islet autoimmunity in T1DM. Except for serving as building blocks membrane biogenesis, accumulative evidence suggests lipids and their derivatives can also modulate different biological processes the progression of T1DM, such inflammation responses, immune attacks, vulnerability. However, types are huge majority them have been largely unexplored In this review, based on classification system, we summarize clinical dyslipidemia related T1DM elucidate potential mechanisms by which they participate regulating modulating lymphocyte function influencing susceptibility apoptosis dysfunction. This review systematically recapitulates role various providing new therapeutic approaches from nutritional perspective.

Language: Английский

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Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus

Journal of Autoimmunity, Journal Year: 2022, Volume and Issue: 132, P. 102863 - 102863

Published: July 16, 2022

Language: Английский

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Phosphatidic Acid Promoting the Generation of Interleukin‐17A Producing Double‐Negative T Cells by Enhancing mTORC1 Signaling in Lupus

Arthritis & Rheumatology, Journal Year: 2024, Volume and Issue: 76(7), P. 1096 - 1108

Published: March 4, 2024

Objective The goal was to investigate the role and intracellular regulatory mechanisms of double‐negative T (DNT) cells in pathogenesis systemic lupus erythematosus (SLE). Methods DNT were assessed murine models, patients with SLE, controls using flow cytometry (FCM). from either resiquimod (R848) or vehicle‐treated C57BL/6 (B6) mice cultured B R848‐treated explore functions. Differential mechanistic target rapamycin (mTOR) pathway signaling measured FCM quantitative polymerase chain reaction validated by inhibition. Candidate lipid metabolites detected liquid chromatography electrospray ionization mass spectrometry/mass spectrometry functionally cell cultures. Results markedly increased both spontaneous induced mouse models SLE. Expanded B6 produced elevated interleukin (IL)‐17A IgG germinal center (GCB) cells. Expansion associated activation mTORC1 that IL‐17A levels number exhibited dose‐dependent reduction treatment. Lipidomics studies revealed differential patterns mice. Among candidate metabolites, phosphatidic acid (PA) partially controlled phospholipase D2 expression downstream p‐S6 positively expanded IL‐17A–producing Similarly, proportions circulating SLE correlated disease activity proteinuria, secretion after vitro PA stimulation. Conclusion accumulation could activate pathway, promoting expansion secretion, resulting GCB abnormalities lupus. image

Language: Английский

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Crucial Roles of RSAD2/viperin in Immunomodulation, Mitochondrial Metabolism and Autoimmune Diseases

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

Published: June 23, 2024

Autoimmune diseases are typically characterized by aberrant activation of immune system that leads to excessive inflammatory reactions and tissue damage. Nevertheless, precise targeted efficient therapies limited. Thus, studies into novel therapeutic targets for the management autoimmune urgently needed. Radical S-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG) renowned antiviral properties protein it encodes, named viperin. An increasing number have underscored new roles RSAD2/viperin in immunomodulation mitochondrial metabolism. Previous shown there a complex interplay between RSAD2/vipeirn mitochondria binding iron-sulfur (Fe-S) cluster necessary involvement viperin Viperin influences proliferation development cells as well inflammation via different signaling pathways. However, function varies comprehensive overview this emerging theme lacking. This review will describe characteristics RSAD2/viperin, decipher its immunometabolic processes, clarify crosstalk mitochondria. Furthermore, we emphasize crucial RSAD2 potential application value.

Language: Английский

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Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: June 25, 2024

Abstract Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that frequently identified with poor prognosis. Macrophages play an important role in its pathogenesis. Different macrophage subtypes have different effects on lupus-affected kidneys. Based their origin, macrophages can be divided into monocyte-derived (MoMacs) tissue-resident (TrMacs). During nephritis, TrMacs develop hybrid pro-inflammatory anti-inflammatory functional phenotype, as they do not secrete arginase or nitric oxide (NO) when stimulated by cytokines. The infiltration these mixed-phenotype related to the continuous damage caused immune complexes exposure circulating inflammatory mediators, which indication failure resolve inflammation. On other hand, MoMacs differentiate M1 M2 cells under cytokine stimulation. are cytokines, while main phenotype essentially promotes tissue repair. Conversely, undergo differentiation response considered whereas primarily Moreover, based expression, further M2a, M2b, M2c phenotypes. M2a participate repair, M2b immunoregulatory properties. Further, memory also advancement LN. Studies demonstrated polarization controlled multiple metabolic pathways, such glycolysis, pentose phosphate pathway, fatty acid oxidation, sphingolipid metabolism, tricarboxylic cycle, arginine metabolism. changes pathways regulated substances fish oil, polyenylphosphatidylcholine, taurine, fumaric acid, metformin, salbutamol, inhibit promote polarization, thereby alleviating

Language: Английский

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