Haem toxicity in the aged spleen impairs T-cell immunity through iron deprivation DOI Open Access

David Ezuz,

Heba Ombashe,

Lana watted

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 5, 2024

Summary Ageing profoundly impacts T cell immunity, compromising vaccine responses, susceptibility to infections, and immunosurveillance. Mechanisms of ageing involve cell-intrinsic alterations interactions with other immune stromal cells 1 . This study investigates how a tissue’s microenvironment influences trajectories, following our discovery varying rates within single host. Spleen-derived lymphocytes exhibited functional decline compared those from lymph nodes, proteomic analysis revealing increased expression haem detoxification iron storage proteins in aged spleen-derived lymphocytes. Exposure the spleen or induced multiple phenotypes young lymphocytes, characterized by reduced proliferation upregulation ectonucleotidases CD39 CD73. Mechanistically, we show that survive hostile maintaining low labile pools resist ferroptosis. Finally, vaccination responses mice were enhanced timed infusions. Our findings underscore trade-off between survival function Recent studies Dysfunctional induce premature solid organs host 2,3 highlight bidirectional relationship their microenvironment. Understanding these mechanisms will inform strategies enhance elderly.

Язык: Английский

The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions DOI Creative Commons
Shuting Wu, Hongyan Peng, Songyang Li

и другие.

Cancer Immunology Research, Год журнала: 2024, Номер 12(6), С. 744 - 758

Опубликована: Март 22, 2024

Abstract ω-3 polyunsaturated fatty acids (PUFA) are known to directly repress tumor development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of PUFA, had an immunomodulatory role in inhibiting growth immunocompetent mice. The number natural killer (NK) cells but not the T or B was decreased by DHA supplementation various tissues under physiologic conditions. Although frequency NK were comparable, IFNγ production both spleen lung increased DHA-supplemented mice mouse B16F10 melanoma model. Single-cell RNA sequencing revealed that promoted effector function oxidative phosphorylation no obvious effects on other immune cells. Using Rag2−/− NK-cell depletion PK136 antibody injection, demonstrated suppression dependent mainly vitro experiments showed enhanced production, CD107a expression, mitochondrial (OXPHOS) activity slightly proliferator-activated receptor gamma coactivator-1α (PGC-1α) protein expression PGC-1α inhibitor SR-18292 cell–specific knockout reversed antitumor DHA. summary, our findings broaden current knowledge how protects against cancer from perspective immunomodulation upregulating signaling–mediated OXPHOS

Язык: Английский

Процитировано

8
Metabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy DOI Creative Commons
Li Liu, Zhao-Zhe Hao, Xi Yang

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 9, 2025

Abstract The complex interplay between cancer progression and immune senescence is critically influenced by metabolic reprogramming in T cells. As cells age, especially within the tumor microenvironment, they undergo significant shifts that may hinder their proliferation functionality. This manuscript reviews how alterations contribute to cell discusses potential therapeutic strategies aimed at reversing these changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, lipid metabolism adjustments could rejuvenate senescent cells, potentially restoring efficacy suppression. review also focuses on significance of with aging further explores future direction metabolism-based immunotherapy

Язык: Английский

Процитировано

0
Restoration of LAMP2A expression in old mice leads to changes in the T cell compartment that support improved immune function DOI Creative Commons
Cara A. Reynolds, Sandra Pelka, Floralba Gjergjova

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(38)

Опубликована: Сен. 11, 2024

Chaperone-mediated autophagy (CMA) is a selective form of that contributes to the maintenance cellular homeostasis. CMA activity declines with age in most tissues and systems, including immune system, due reduction levels lysosome-associated membrane protein type 2A (LAMP2A), an essential component. In this study, we show overexpressing copy hLAMP2A within T cells since middle-age can prevent some their age-associated loss function. Our data support idea preserving LAMP2A expression through genetic means leads enhanced proliferative responses, decreased number regulatory cell populations, down-regulated inhibitory receptors by cells. During aging, elevated numbers these immunosuppressive populations significantly contribute downregulation responses. Using comparative proteomics, confirm preservation old mice prevents age-related changes both resting activated proteome. We also explore effect using first-in-class small molecule activators demonstrate improved response upon administration mice. conclude sustaining constitutes potentially viable therapeutic approach improving function age.

Язык: Английский

Процитировано

3
Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells DOI Creative Commons
Xingyue Wang, Chengyu Zhang, Jiahong Su

и другие.

Aging and Disease, Год журнала: 2024, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2024

The process of aging, which involves progressive changes in the body over time, is closely associated with development age-related diseases. Cellular senescence a pivotal hallmark and mechanism aging process. accumulation senescent cells can significantly contribute to onset diseases, thereby compromising overall health. Conversely, elimination enhances body's regenerative reparative capacity, retarding Here, we present brief overview 12 Hallmarks subsequently emphasize potential immune checkpoint blockade, innate cell therapy (including T cells, iNKT macrophages, NK cells), as well CAR-T for inducing augmenting responses aimed at eliminating cells. In addition also explore possibility engineered such CAR-NK CAR-M eliminate summary, immunotherapy, an emerging strategy treatment offers new prospects research.

Язык: Английский

Процитировано

1
Haem toxicity in the aged spleen impairs T-cell immunity through iron deprivation DOI Open Access

David Ezuz,

Heba Ombashe,

Lana watted

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 5, 2024

Summary Ageing profoundly impacts T cell immunity, compromising vaccine responses, susceptibility to infections, and immunosurveillance. Mechanisms of ageing involve cell-intrinsic alterations interactions with other immune stromal cells 1 . This study investigates how a tissue’s microenvironment influences trajectories, following our discovery varying rates within single host. Spleen-derived lymphocytes exhibited functional decline compared those from lymph nodes, proteomic analysis revealing increased expression haem detoxification iron storage proteins in aged spleen-derived lymphocytes. Exposure the spleen or induced multiple phenotypes young lymphocytes, characterized by reduced proliferation upregulation ectonucleotidases CD39 CD73. Mechanistically, we show that survive hostile maintaining low labile pools resist ferroptosis. Finally, vaccination responses mice were enhanced timed infusions. Our findings underscore trade-off between survival function Recent studies Dysfunctional induce premature solid organs host 2,3 highlight bidirectional relationship their microenvironment. Understanding these mechanisms will inform strategies enhance elderly.

Язык: Английский

Процитировано

0