A5029230811- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
- Immune cells in cancer
- Iron Metabolism and Disorders
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Hemoglobinopathies and Related Disorders
- Advanced Glycation End Products research
- Pancreatitis Pathology and Treatment
- Genomics, phytochemicals, and oxidative stress
- CAR-T cell therapy research
- Clinical Nutrition and Gastroenterology
- Atherosclerosis and Cardiovascular Diseases
- COVID-19 Clinical Research Studies
- Renal and related cancers
- Autophagy in Disease and Therapy
University of Michigan–Ann Arbor
2017-2024
University of California, San Diego
2024
Michigan United
2018-2021
Significance The role of cellular metabolism in conventional T cell fate and functions has been established, but little is understood about how metabolic pathways nutrient requirements are controlled natural killer (NKT) cells. present study shows that, unlike CD4 cells, activation NKT cells metabolize glucose to the pentose phosphate pathway TCA cycle instead converting into lactate. In line with this, a high lactate microenvironment detrimental for homeostasis effector function. Glucose...
Iron has long been established as a critical mediator of T cell development and proliferation. However, the mechanisms by which iron controls CD4 activation expansion remain poorly understood. In this study, we show that stimulation cells from C57BL/6 mice not only decreases total labile levels but also leads to changes in expression homeostatic machinery. Additionally, restraining availability vitro severely inhibited proliferation cycle progression. Although modulating cellular increased...
Abstract Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological pathological conditions as second messengers. ROS essential for activation T cells, but how influence NKT cells is unknown. In the present study, we investigated role in cell function. We found that not CD4 or CD8 have dramatically high spleen liver mice thymus adipose tissues. Accordingly, ROS-high exhibited increased susceptibility apoptotic death with oxidative stress. High...
Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) proteins work in concert to regulate the levels of reactive oxygen species (ROS). The Keap1-Nrf2 antioxidant system also participates T cell differentiation inflammation, but its role innate development functions remains unclear. We report that cell-specific deletion Keap1 results defective reduced numbers invariant natural killer (NKT) cells thymus peripheral organs a cell-intrinsic manner....
Natural killer T (NKT) cells operate distinctly different metabolic programming from CD4 cells, including a strict requirement for glutamine to regulate cell homeostasis. However, the underlying mechanisms remain unknown. Here, we report that at steady state, NKT have higher levels than and increase glutaminolysis on activation. Activated use fuel tricarboxylic acid cycle glutathione synthesis. In addition, glutamine-derived nitrogen enables protein glycosylation via hexosamine biosynthesis...
In response to an immune challenge, naive T cells undergo a transition from quiescent activated state acquiring the effector function. Concurrently, these reprogram cellular metabolism, which is regulated by iron. We and others have shown that iron homeostasis controls proliferation mitochondrial function, but underlying mechanisms are poorly understood. Given derived heme makes up large portion of pool, we investigated in using mice with cell-specific deletion exporter, FLVCR1 [referred as...
Abstract Cellular metabolism is critical for generating energy and macromolecules cell growth survival. In recent years, the importance of in mediating T differentiation, proliferation, function has been a hot topic investigation. However, very little known about metabolic regulation invariant natural killer (iNKT) cells. this viewpoint, we will discuss what currently immunometabolism iNKT cells how these findings relate to CD4
Abstract The E3 ubiquitin ligase cullin 3 (Cul3) is critical for invariant NKT (iNKT) cell development, as iNKT cells lacking Cul3 accumulate in the immature developmental stages. However, mechanisms by which mediates development remain unknown. In this study, we investigated role of both and mature thymic using a mouse model with T cell–specific deletion Cul3. We found that proliferated died more than wild-type did. These also displayed increased glucose metabolism autophagy. Interestingly,...
Abstract Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological pathological conditions as second messengers. ROS essential for antigen specific activation T cells, but little is known about what role play in NKT cells. In the current study, we investigated cell function. We found that levels similar among CD4, CD8 subsets thymus. However, neither CD4 nor showed dramatically increased spleen liver not adipose tissues. peripheral cells were...
Abstract Cellular metabolism is essential in dictating conventional T cell development and function, but its role natural killer (NKT) cells has not been well studied. We have previously shown that NKT operate distinctly different metabolic programming from CD4 cells, including a strict requirement for glutamine to regulate homeostasis. However, the mechanisms by which their homeostasis effector functions remain unknown. In this study, we report steady state higher levels than increase...
Abstract Cellular metabolism controlled by the signaling pathways has a crucial role in dictating outcome of T cell activation and effector function. Reactive oxygen species (ROS) are byproducts aerobic contribute to both physiological pathological conditions as second messenger. In cells, ROS levels increase upon antigen specific responses cells compromised absence production mitochondria. However, it is not well understood how NKT cells’ functions metabolism. current study, we investigated...
Abstract Cellular metabolism and signaling pathways are the key regulators to determine T cell fate, survival function, particularly during activation. Resting CD4 CD8 cells use oxidative phosphorylation as a primary energy source but switches glycolysis upon activation, which is necessary produce biomolecules for proliferation function. Failure of this reprogramming detrimental mediated immunity. However, little understood about how NKT control their survive We found that operate distinctly...
Abstract Kelch-like ECH-associated protein (Keap1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) proteins work in concert as anti-oxidant system to regulate reactive oxygen species (ROS) levels. Additionally, Keap1-Nrf2 has been shown play a role T cell-mediated inflammation but its for maintenance function of innate cells is unclear. Using mice with T-cell specific deletion Keap1 (KO) leading higher Nrf2 activity, we recently reported that plays an essential the development...
Abstract Cellular metabolism is essential in dictating conventional T cell development and function, but its role natural killer (NKT) cells has not been well studied. We have previously shown that NKT operate distinctly different metabolic programming from CD4 cells, including a strict requirement for glutamine to regulate homeostasis. However, the mechanisms by which their homeostasis effector functions remain unknown. In this study, we report steady state higher levels than increase...
Abstract Cellular metabolism is essential in dictating T cell development and function, but its role natural killer (NKT) cells has not been well studied. Activated CD4 undergo a metabolic switch from oxidative to glycolytic fuel their proliferation effector function. We have previously shown that NKT operate distinctly different programming cells. found that, unlike cells, rely more on glutamine for homeostasis. In fact, we observed resting higher levels of glutamine-derived metabolites...