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1.
Annu Rev Immunol ; 41: 181-205, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37126417

RESUMO

There is a dramatic remodeling of the T cell compartment during aging. The most notorious changes are the reduction of the naive T cell pool and the accumulation of memory-like T cells. Memory-like T cells in older people acquire a phenotype of terminally differentiated cells, lose the expression of costimulatory molecules, and acquire properties of senescent cells. In this review, we focus on the different subsets of age-associated T cells that accumulate during aging. These subsets include extremely cytotoxic T cells with natural killer properties, exhausted T cells with altered cytokine production, and regulatory T cells that gain proinflammatory features. Importantly, all of these subsets lose their lymph node homing capacity and migrate preferentially to nonlymphoid tissues, where they contribute to tissue deterioration and inflammaging.


Assuntos
Envelhecimento , Subpopulações de Linfócitos T , Humanos , Animais , Linfócitos T Reguladores , Diferenciação Celular
2.
Nat Aging ; 3(5): 475-476, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37198439
3.
Br J Pharmacol ; 179(9): 1839-1856, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33817782

RESUMO

Metabolism is dynamically regulated to accompany immune cell function, and altered immunometabolism can result in impaired immune responses. Concomitantly, the pharmacological manipulation of metabolic processes offers an opportunity for therapeutic intervention in inflammatory disorders. The nicotinamide adenine dinucleotide (NAD+ ) is a critical metabolic intermediate that serves as enzyme cofactor in redox reactions, and is also used as a co-substrate by many enzymes such as sirtuins, adenosine diphosphate ribose transferases and synthases. Through these activities, NAD+ metabolism regulates a broad spectrum of cellular functions such as energy metabolism, DNA repair, regulation of the epigenetic landscape and inflammation. Thus, the manipulation of NAD+ availability using pharmacological compounds such as NAD+ precursors can have immune-modulatory properties in inflammation. Here, we discuss how the NAD+ metabolism contributes to the immune response and inflammatory conditions, with a special focus on multiple sclerosis, inflammatory bowel diseases and inflammageing. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.


Assuntos
NAD , Sirtuínas , Autoimunidade , Metabolismo Energético , Imunidade , NAD/metabolismo , Sirtuínas/metabolismo
4.
Nat Rev Immunol ; 22(2): 97-111, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34099898

RESUMO

Age-related T cell dysfunction can lead to failure of immune tolerance mechanisms, resulting in aberrant T cell-driven cytokine and cytotoxic responses that ultimately cause tissue damage. In this Review, we discuss the role of T cells in the onset and progression of age-associated conditions, focusing on cardiovascular disorders, metabolic dysfunction, neuroinflammation and defective tissue repair and regeneration. We present different mechanisms by which T cells contribute to inflammageing and might act as modulators of age-associated diseases, including through enhanced pro-inflammatory and cytotoxic activity, defective clearance of senescent cells or regulation of the gut microbiota. Finally, we propose that 'resetting' immune system tolerance or targeting pathogenic T cells could open up new therapeutic opportunities to boost resilience to age-related diseases.


Assuntos
Microbioma Gastrointestinal , Linfócitos T , Envelhecimento , Citocinas , Microbioma Gastrointestinal/fisiologia , Humanos , Tolerância Imunológica
5.
FEBS J ; 287(16): 3350-3369, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32255251

RESUMO

The inflammatory response involves the activation of several cell types to fight insults caused by a plethora of agents, and to maintain the tissue homoeostasis. On the one hand, cells involved in the pro-inflammatory response, such as inflammatory M1 macrophages, Th1 and Th17 lymphocytes or activated microglia, must rapidly provide energy to fuel inflammation, which is essentially accomplished by glycolysis and high lactate production. On the other hand, regulatory T cells or M2 macrophages, which are involved in immune regulation and resolution of inflammation, preferentially use fatty acid oxidation through the TCA cycle as a main source for energy production. Here, we discuss the impact of glycolytic metabolism at the different steps of the inflammatory response. Finally, we review a wide variety of molecular mechanisms which could explain the relationship between glycolytic metabolites and the pro-inflammatory phenotype, including signalling events, epigenetic remodelling, post-transcriptional regulation and post-translational modifications. Inflammatory processes are a common feature of many age-associated diseases, such as cardiovascular and neurodegenerative disorders. The finding that immunometabolism could be a master regulator of inflammation broadens the avenue for treating inflammation-related pathologies through the manipulation of the vascular and immune cell metabolism.


Assuntos
Ciclo do Ácido Cítrico/imunologia , Glicólise/imunologia , Inflamação/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Linfócitos T Reguladores/imunologia , Animais , Humanos , Inflamação/metabolismo , Macrófagos/classificação , Macrófagos/metabolismo , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/metabolismo
6.
Cells ; 9(1)2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31905682

RESUMO

Mitochondrial metabolism and autophagy are two of the most metabolically active cellular processes, playing a crucial role in regulating organism longevity. In fact, both mitochondrial dysfunction or autophagy decline compromise cellular homeostasis and induce inflammation. Calorie restriction (CR) is the oldest strategy known to promote healthspan, and a plethora of CR mimetics have been used to emulate its beneficial effects. Herein, we discuss how CR and CR mimetics, by modulating mitochondrial metabolism or autophagic flux, prevent inflammatory processes, protect the intestinal barrier function, and dampen both inflammaging and neuroinflammation. We outline the effects of some compounds classically known as modulators of autophagy and mitochondrial function, such as NAD+ precursors, metformin, spermidine, rapamycin, and resveratrol, on the control of the inflammatory cascade and how these anti-inflammatory properties could be involved in their ability to increase resilience to age-associated diseases.


Assuntos
Autofagia , Biomimética , Restrição Calórica , Inflamação/metabolismo , Mitocôndrias/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Autofagia/efeitos dos fármacos , Suscetibilidade a Doenças , Metabolismo Energético , Homeostase , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Mitocôndrias/efeitos dos fármacos
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