Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4+ T Cells of an Autoimmune Uveitis Model DOI Open Access

Ronja Söth,

Anne Lisbeth Hoffmann,

Cornelia A. Deeg

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11513 - 11513

Published: Oct. 26, 2024

Equine recurrent uveitis (ERU) is a spontaneously occurring autoimmune disease and one of the leading causes blindness in horses worldwide. Its similarities to autoimmune-mediated humans make it unique spontaneous animal model for this disease. Although many aspects ERU pathogenesis have been elucidated, remains not fully understood requires further research. CD4+ T cells particular focus In previous study, we showed metabolic alterations from cases, including an increased basal oxygen consumption rate (OCR) elevated compensatory glycolysis. To investigate underlying reasons consequences these changes, quantified reactive species (ROS) production cases compared healthy controls, revealing significantly higher ROS ERU-affected horses. Additionally, aimed define mitochondrial fuel oxidation glucose, glutamine, long-chain fatty acids (LCFAs) identified significant differences between controls. lower dependency on glucose greater flexibility LCFAs, indicating enhanced ability switch alternative fuels when necessary.

Language: Английский

Metabolic regulation of the immune system in health and diseases: mechanisms and interventions DOI Creative Commons
Tengyue Hu, Changhai Liu, Min Lei

et al.

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

Citations

29
Intestinal tissue-resident memory T cells: Characteristics, functions under physiological and pathological conditions and spatial specificity DOI Creative Commons

Ruilan Yan,

Dingjiacheng Jia, Yinliang Qi

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Tissue-resident memory T (TRM) cells are a distinct subset of that persist in non-lymphoid tissues, providing localized and rapid immune responses to infection malignancy. Unlike circulating cells, TRM have unique homing functional characteristics shaped by the tissue microenvironment. In gut, play pivotal role maintaining mucosal immunity, exhibiting phenotypic heterogeneity different intestinal compartments response aging pathological conditions. This review aims systematically examine definition, spatial roles (iTRM) cells. It highlights their contributions physiological involvement processes such as inflammatory bowel disease (IBD) colorectal cancer (CRC), age-related dynamics. The also explores emerging therapeutic implications modulating iTRM for health management. KEY SCIENTIFIC CONCEPTS OF REVIEW: defined surface markers like CD69 CD103, transcriptional regulators Hobit, Runx3, Blimp-1, well cytokine signals including TGF-β, IFN-β, IL-12. They exhibit across layers (epithelium versus lamina propria) regions (small intestine colon). IBD, dual role, contributing both inflammation repair, whereas CRC, specific subsets (e.g., CD8+ CD103+ CD39+) associated with enhanced antitumor immunity. Aging impacts functionality, shifts CD4+/CD8+ ratio reduced production elderly individuals. Insights into metabolic, transcriptional, environmental regulation provide avenues targeted therapies diseases, immunotherapy, interventions delay aging.

Language: Английский

Citations

1
Calcium Release-Activated Calcium Modulator ORAI1-Sensitive Serine Dehydratase Regulates Fatty Acid-Induced CD4+ Th17/Treg Imbalance in Dairy Cows DOI Creative Commons
Bingbing Zhang, Jingjing Wang,

Ming Li

et al.

Animals, Journal Year: 2025, Volume and Issue: 15(3), P. 388 - 388

Published: Jan. 30, 2025

High concentrations of free fatty acids (FFAs) caused by negative energy balance render the cow more prone to inflammatory diseases in part due an imbalance types immune cells and their specific functions. We previously demonstrated that ORAI calcium release-activated modulator 1 (ORAI1) was associated with increased CD4+ Th17 content, but precise mechanisms remain unclear. The purpose this study evaluate efficacy FFAs on T cell response. dairy cows transcript level pro-inflammatory factor IL-17A, plasma concentration amount intracellular IL-17A increase while levels anti-inflammatory FOXP3 were downregulated. These changes indicated Th17/Treg inflammation high FFA. Moreover, ORAI1 SDS abundance elevated transcriptomics, QPCR, Western blot. Knockdown (siSDS) did not alter expression from high-FFA cows, it decreased factors. Transfection using siRNA knockdown for (siORAI1) revealed decreased. Serine can be catabolized pyruvate action serine dehydratase (SDS). Data suggested after calving regulates via SDS, does regulate abundance. above data a mechanism regulated ORAI1-sensitive pathway early postpartum experiencing conditions. Thus, targeting may represent new therapeutic interventional approach preventing immune-related disorders around parturition.

Language: Английский

Citations

0
The influence of fatty acid metabolism on T cell function in lung cancer DOI Open Access
Jessica Petiti, Ludovica Arpinati, Alessio Menga

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

The tumor microenvironment (TME) is a complex ecosystem, encompassing variety of cellular and non-cellular elements surrounding interacting with cancer cells, overall promoting growth, immune evasion, therapy resistance. In the context solid tumors, factors, such as hypoxia, nutritional competition, increased stress responses, glucose demand, PD-1 signals strongly influence metabolic alterations in TME, highly contributing to maintenance tumor-supportive immune-suppressive milieu. Cancer cell-induced partly result an fatty acid (FA) metabolism within which favors recruitment M2 macrophages myeloid-derived suppressor crucial contributors T-cell exhaustion, exclusion, decreased effector functions. drastic pro-tumoral changes induced by rewiring signaling loops that support progression metastatic spreading, negatively impact efficacy. As tumor- are increasingly gaining attention due their potential therapeutic implications, we discuss effects altered lipid on progression, response, efficacy lung cancer. particular, focus our analysis tumor-induced experienced T lymphocytes possible strategies overcome immunotherapy resistance targeting specific pathways cells.

Language: Английский

Citations

0
Metabolic reprogram and T cell differentiation in inflammation: current evidence and future perspectives DOI Creative Commons
Yuxin Shi, Hao Zhang, Changhong Miao

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 28, 2025

T cell metabolism and differentiation significantly shape the initiation, progression, resolution of inflammatory responses. Upon activation, cells undergo extensive metabolic shifts to meet distinct functional demands across various stages. These alterations are not only critical for defining different subsets, but also sustaining their activity in environments. Key signaling pathways-including mTOR, HIF-1α, AMPK regulate these adaptions, linking cellular energy states with fate decisions. Insights into regulation offer potential therapeutic strategies manipulate function, implications treating autoimmune diseases, chronic inflammation, cancer by targeting specific pathways.

Language: Английский

Citations

0
Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4+ T Cells of an Autoimmune Uveitis Model DOI Open Access

Ronja Söth,

Anne Lisbeth Hoffmann,

Cornelia A. Deeg

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11513 - 11513

Published: Oct. 26, 2024

Equine recurrent uveitis (ERU) is a spontaneously occurring autoimmune disease and one of the leading causes blindness in horses worldwide. Its similarities to autoimmune-mediated humans make it unique spontaneous animal model for this disease. Although many aspects ERU pathogenesis have been elucidated, remains not fully understood requires further research. CD4+ T cells particular focus In previous study, we showed metabolic alterations from cases, including an increased basal oxygen consumption rate (OCR) elevated compensatory glycolysis. To investigate underlying reasons consequences these changes, quantified reactive species (ROS) production cases compared healthy controls, revealing significantly higher ROS ERU-affected horses. Additionally, aimed define mitochondrial fuel oxidation glucose, glutamine, long-chain fatty acids (LCFAs) identified significant differences between controls. lower dependency on glucose greater flexibility LCFAs, indicating enhanced ability switch alternative fuels when necessary.

Language: Английский

Citations

1