Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(3), P. e1011165 - e1011165

Published: March 7, 2023

Stimulation of naïve T cells during primary infection or vaccination drives the differentiation and expansion effector memory that mediate immediate long-term protection. Despite self-reliant rescue from infection, BCG vaccination, treatment, is rarely established against Mycobacterium tuberculosis ( M . tb ) resulting in recurrent (TB). Here, we show berberine (BBR) enhances innate defense mechanisms stimulates Th1/Th17 specific (T EM ), central CM tissue-resident RM responses leading to enhanced host protection drug-sensitive drug-resistant TB. Through whole proteome analysis human PBMCs derived PPD + healthy individuals, identify BBR modulated NOTCH3/PTEN/AKT/FOXO1 pathway as mechanism elevated CD4 cells. Moreover, BBR-induced glycolysis resulted functions superior murine This regulation cell by remarkably BCG-induced anti-tubercular immunity lowered rate TB recurrence due relapse re-infection. These results thus suggest tuning immunological a feasible approach augment resistance unveil potential adjunct immunotherapeutic immunoprophylactic

Language: Английский

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Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2010 - 2010

Published: Jan. 19, 2023

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness in which individuals are plagued with fatigue, inflammatory symptoms, cognitive dysfunction, and the hallmark symptom, post-exertional malaise. While cause of this disease remains unknown, there evidence potential infectious component that, along patient symptoms common onsets disease, implicates immune system dysfunction. To further our understanding state ME/CFS lymphocytes, we characterized role fatty acids isolated Natural Killer cells, CD4+ T CD8+ cells circulation after overnight stimulation, through implicit perturbations to acid oxidation. We examined samples obtained from at least 8 as many 20 subjects for cell characterization variety experiments found that all three types increased their utilization lipids levels pertinent proteins involved metabolic pathway samples, particularly during higher energy demands activation. In populations contributing these shifts, included memory effector naïve cells. also discovered patients healthy control had significant correlations between measurements metabolism demographic data. These findings provide support dysfunction hypothesize about consequences altered fuel dependencies may have on NK function, shed light illness's mechanism action.

Language: Английский

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Mitochondrial Dysfunction: At the Nexus between Alcohol-Associated Immunometabolic Dysregulation and Tissue Injury

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8650 - 8650

Published: May 12, 2023

Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such ATP synthesis initiation apoptosis. However, current research has provided evidence that mitochondria participate myriad cellular processes, immune activation, nutrient sensing pancreatic β-cells, muscle stem progenitor cell differentiation. The literature indicates alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation disrupting dynamics, leading to dysfunctional accumulation. As discussed this review, dyshomeostasis emerges at nexus between alcohol-disrupted tissue injury. Here, we highlight link focus on alcohol-mediated disruption immunometabolism, which refers two distinct, yet interrelated processes. Extrinsic immunometabolism involves processes whereby cells products influence and/or metabolism. Intrinsic describes fuel utilization bioenergetics affect intracellular Alcohol-induced dysregulation cells, contributing This review will present state literature, describing metabolic immunometabolic from perspective.

Language: Английский

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Genetically engineering glycolysis in T cells increases their antitumor function

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(7), P. e008434 - e008434

Published: July 1, 2024

Background T cells play a central role in the antitumor response. However, they often face numerous hurdles tumor microenvironment, including scarcity of available essential metabolites such as glucose and amino acids. Moreover, cancer can monopolize these resources to thrive proliferate by upregulating metabolite transporters maintaining high metabolic rate, thereby outcompeting cells. Methods Herein, we sought improve T-cell function vicinity enhancing their glycolytic capacity better compete with To achieve this, engineered human express key glycolysis enzyme, phosphofructokinase, conjunction Glucose transporter 3, transporter. We co-expressed these, along tumor-specific chimeric antigen or receptors. Results Engineered demonstrated an increased cytokine secretion upregulation activation markers compared control displayed superior capacity, which translated into improved vivo therapeutic potential xenograft model tumors. Conclusion In summary, findings support implementation engineering enhance efficacy cellular immunotherapies for cancer.

Language: Английский

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Fatty Acid Oxidation Promotes Apoptotic Resistance and Proinflammatory Phenotype of CD4+ Tissue-resident Memory T cells in Crohn’s Disease

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 17(6), P. 939 - 964

Published: Jan. 1, 2024

CD patients.Targeting FAO of CD4 + TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in Patients.Conclusion: process an accelerated mediated by activated NF-κB signaling patients, targeting could reverse phenotype.These findings shed a new light on the pathogenic mechanism investigation novel therapy development patients.

Language: Английский

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