PLZF expression in adipose resident natural killer T cells
PLZF 在脂肪驻留自然杀伤 T 细胞中的表达
基本信息
- 批准号:10364677
- 负责人:
- 金额:$ 19.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-08 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AdipocytesAdipose tissueAnti-Inflammatory AgentsAntigen-Presenting CellsCell physiologyCellsChronicCollaborationsCytotoxic T-LymphocytesDataDevelopmentDietDown-RegulationEatingEnvironmentFOXP3 geneFatty acid glycerol estersFrequenciesFutureHumanImmune systemImmunomodulatorsInflammationInflammatory ResponseInsulin ResistanceLearningLipidsMetabolicMetabolic DiseasesMetabolic PathwayMetabolismMolecularMusObesityPopulationPopulation SizesProteinsRegulationRegulatory T-LymphocyteSiteSpleenThymus GlandTissuesVariantWeight GainWild Type MouseZNF145 genecell typecytokineeffector T cellgood dietinnovationinsightmacrophagemouse modelpreventpromotertranscription factor
项目摘要
Project Summary
Adipose tissue is a site where the immune system and metabolic pathways intersect. Adipocytes are now
recognized as antigen presenting cells for lipids and likely directly activate natural killer T cells (NKT cells) via
CD1d. NKT cells are potent modulators of the immune system that are able to regulate the function of other
cell types largely by their capacity to rapidly produce large amounts of a wide variety of cytokines. Recent data
show that adipose resident NKT cells (arNKT cells) modulate diet-induced weight gain and influence
metabolism. When eating a calorically balanced diet, arNKT cells appear to encourage adipocytes to maintain
a healthy tissue environment and prevent insulin resistance.
Nearly all of the innate-like functions of NKT cells are dependent upon the BTB-ZF transcription factor, PLZF
(zbtb16). Therefore, it is surprising that arNKT cells do not express PLZF. To our knowledge, this is the only
population of NKT cells that does not continuously express the transcription factor. Chronic inflammation is
associated with weight gain and subsequent metabolic disease. arNKT cells were shown to induce an anti-
inflammatory response both by modulating macrophage functions and by impacting the frequency, proliferation
and function of FoxP3-expressing Tregs. We propose that altered PLZF expression will impact these arNKT
cell functions, which in turn, will alter the metabolism of white adipose tissue. Our studies will determine if
changes in PLZF expression in arNKT cells alters their ability to control obesity and metabolic changes.
We will use an innovative array of genetically modified mouse models that allow for variation in the levels of
PLZF expression. We hypothesize that PLZF protein levels are essential for the control of arNKT cell functions
and if the levels are altered, the onset of obesity and metabolic disease will increase. Data supporting this
conclusion will lead to future studies to determine if variability in PLZF expression in humans is potentially a
contributing factor to obesity. Importantly, analysis of arNKT cells that do not function correctly is expected to
reveal new information about the mechanisms by which arNKT cells normally function.
项目摘要
脂肪组织是免疫系统和代谢途径交叉的部位。脂肪细胞现在
被认为是脂质的抗原呈递细胞,并可能通过以下途径直接激活自然杀伤T细胞(NKT细胞):
CD1d。NKT细胞是免疫系统的有效调节剂,其能够调节其他免疫系统的功能。
细胞类型主要是通过它们快速产生大量各种细胞因子的能力。最近的数据
显示了脂肪驻留NKT细胞(arNKT细胞)调节饮食诱导的体重增加并影响
新陈代谢.当进食热量平衡的饮食时,arNKT细胞似乎鼓励脂肪细胞维持
健康的组织环境和防止胰岛素抵抗。
NKT细胞的几乎所有先天性功能都依赖于BTB-ZF转录因子PLZF
(zbtb16)。因此,令人惊讶的是arNKT细胞不表达PLZF。据我们所知,这是唯一的
不连续表达转录因子的NKT细胞群。慢性炎症是
与体重增加和随后的代谢疾病有关。arNKT细胞显示出诱导抗-
通过调节巨噬细胞功能和通过影响频率、增殖
和表达FoxP 3的T细胞的功能。我们认为PLZF表达的改变会影响这些arNKT,
细胞功能,这反过来又会改变白色脂肪组织的代谢。我们的研究将决定
arNKT细胞中PLZF表达的变化改变了它们控制肥胖和代谢变化的能力。
我们将使用一系列创新的转基因小鼠模型,这些小鼠模型允许不同水平的
PLZF表达。我们假设PLZF蛋白水平对于控制arNKT细胞功能是必需的。
如果水平发生变化,肥胖和代谢疾病的发病率就会增加。支持这一点的数据
结论将导致未来的研究,以确定是否在人类PLZF表达的变异是潜在的,
导致肥胖的因素。重要的是,对不能正确发挥功能的arNKT细胞的分析预计将有助于
揭示了arNKT细胞正常功能机制的新信息。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Derek B. Sant'Angelo其他文献
Derek B. Sant'Angelo的其他文献
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{{ truncateString('Derek B. Sant'Angelo', 18)}}的其他基金
PLZF expression in adipose resident natural killer T cells
PLZF 在脂肪驻留自然杀伤 T 细胞中的表达
- 批准号:
10189318 - 财政年份:2021
- 资助金额:
$ 19.63万 - 项目类别:
Contribution of Innate-like Tregs for Preventing Tissue Inflammation
先天性 Tregs 对预防组织炎症的贡献
- 批准号:
10412729 - 财政年份:2021
- 资助金额:
$ 19.63万 - 项目类别:
Expression of BTB-ZF Transcriptional Regulators as Biomarkers of Immune System Development
BTB-ZF 转录调节因子的表达作为免疫系统发育的生物标志物
- 批准号:
9092587 - 财政年份:2016
- 资助金额:
$ 19.63万 - 项目类别:
Control of cytokine production by human NK cells
控制人类 NK 细胞产生细胞因子
- 批准号:
8987712 - 财政年份:2015
- 资助金额:
$ 19.63万 - 项目类别:
Leukocyte subset identification by single cell analysis of BTB-ZF gene
通过 BTB-ZF 基因的单细胞分析鉴定白细胞亚群
- 批准号:
8705813 - 财政年份:2013
- 资助金额:
$ 19.63万 - 项目类别:
Leukocyte subset identification by single cell analysis of BTB-ZF gene
通过 BTB-ZF 基因的单细胞分析鉴定白细胞亚群
- 批准号:
8444930 - 财政年份:2013
- 资助金额:
$ 19.63万 - 项目类别:
Immunobiology of NKT cell development and function
NKT 细胞发育和功能的免疫生物学
- 批准号:
8099344 - 财政年份:2010
- 资助金额:
$ 19.63万 - 项目类别:
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