Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Priceman, Saul J.; Kujawski, Maciej; Shen, Shudan; Cherryholmes, Gregory; Lee, Heehyoung; Zhang, Chunyan; Kruper, Laura; Mortimer, Joanne; Jove, Richard; Riggs, Arthur D.; Yu, Hua

doi:10.1073/pnas.1311557110

Cited by 107 publications

(106 citation statements)

References 40 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…**p , 0.01, *p , 0.05. cells, especially in pathological settings (66)(67)(68). In addition, the production of these cytokines was shown to be pathologically dysregulated in the obese state, contributing to insulin resistance (9,43,(69)(70)(71)(72).…”

Section: Discussionmentioning

confidence: 99%

ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity

Pandolfi

Ferraro

Sananez

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Obesity-induced inflammation is conducted by a metabolic pathway, which eventually causes activation of specialized immune cells and leads to an unresolved inflammatory response within the tissue. For this reason, it is critically important to determine how hypertrophic fat tissue alters T cell balance to drive inflammation. In this study, we identify the purinergic signaling as a novel mechanism driving the adaptive Th17 response in human visceral adipose tissue (VAT) of metabolically unhealthy obese patients. We demonstrate that ATP acting via the P2X7 receptor pathway promotes a Th17 polarizing microenvironment with high levels of IL-1β, IL-6, and IL-17 in VAT explants from lean donors. Moreover, in vitro blockade of the P2X7 receptor abrogates the levels of these cytokines. These findings are consistent with a greater frequency of Th17 cells in tissue from metabolically unhealthy obese donors, revealed not only by the presence of a baseline Th17-promoting milieu, but also by the higher expression of steadily recognized Th17 markers, such as RORC, IL-17 cytokine, and IL-23R, in comparison with metabolically healthy obese and lean donors. In addition, we demonstrate that CD39 expression on CD4+ effector T cells represents a novel Th17 marker in the inflamed VAT, which also confers protection against ATP-induced cell death. The manipulation of the purinergic signaling might represent a new therapeutic target to shift the CD4+ T cell balance under inflammatory conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity

Pandolfi

Ferraro

Sananez

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…During the development of diet-induced obesity (DIO), the number of AT T cells increases as does the CD8 + -to-CD4 + T-cell ratio, whereas the percentage of Tregs decreases dramatically (14)(15)(16). This change in Tcell subsets is mediated by the expression of Stat3 (17). CD8 + cells seem to precede macrophage infiltration and promote the recruitment of AT macrophages by secreting MCP-1, MCP-3, and RANTES (regulated on activation, normal T cell expressed and secreted) (18).…”

Section: Immune Cells Orchestrate the Outcome Of At Inflammationmentioning

confidence: 99%

“…LIGHT binds to HVEM (herpes simplex virus glycoprotein D for herpesvirus entry mediator, TNFRSF14), which is expressed on activated and resting immune cells, adipocytes, and endothelial cells. LIGHT-HVEM interactions induce a strong activation of NF-kB that results in T-cell activation and expansion and the secretion of proinflammatory mediators such as adhesion molecules, chemokines, and matrix metalloproteinases (17,37).…”

Section: Light-hvemmentioning

confidence: 99%

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

et al. 2014

View full text Add to dashboard Cite

In the past two decades, numerous experimental and clinical studies have established the importance of inflammation and immunity in the development of obesity and its metabolic complications, including insulin resistance and type 2 diabetes mellitus. In this context, T cells orchestrate inflammatory processes in metabolic organs, such as the adipose tissue (AT) and liver, thereby mediating obesity-related metabolic deterioration. Costimulatory molecules, which are present on antigen-presenting cells and naïve T cells in the AT, are known to mediate the crosstalk between the adaptive and innate immune system and to direct T-cell responses in inflammation. In this Perspectives in Diabetes article, we highlight the newest insights in immune cell interactions in obesity and discuss the role of costimulatory dyads in its pathogenesis. Moreover, the potential of therapeutic strategies that target costimulatory molecules in the metabolic syndrome is explored.

show abstract

“…In addition, the STAT protein family is a group of transcription factors that are found in diverse organisms, ranging from flatworms to humans. In particular, STAT3 regulates diverse target pathways involved in bone formation (Zhou et al, 2011) and adipocyte differentiation (Priceman et al, 2013), which is important for body measurement and carcass quality traits in livestock.…”

Section: Discussionmentioning

confidence: 99%

Identification of single nucleotide polymorphisms of the signal transducer and activator of transcription 3 gene (STAT3) associated with body measurement and carcass quality traits in beef cattle

Song¹,

Gui²,

Xu³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Previous studies have shown that the signal transducer and activator of transcription 3 gene (STAT3) is involved in lipid storage and energy metabolism, suggesting that STAT3 is a potential candidate gene that affects body measurement and carcass quality traits in animals. Therefore, the aim of this study was to identify polymorphisms in bovine STAT3 and to analyze their possible associations with body measurement and carcass quality traits in 493 individuals of 2 native Chinese cattle breeds: Qinchuan (N = 371) and Jiaxian cattle (N = 122). DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were employed to detect STAT3 single nucleotide polymorphisms (SNPs). We found 5 SNPs: 1 in an exon (g.65812G>A: exon 16) and 4 in introns (g.43591G>A: 13 intron, g.67492T>G: 19 intron, g.67519T>C: 19 intron, and g.68964G>A: 20 intron). Both g.65812G>A and g.68964G>A were not in HardyWeinberg equilibrium (HWE), whereas individual frequencies of each genotype were consistent with HWE for other SNPs in Qinchuan cattle populations. For the Jiaxian cattle, the genotype distributions of the 4 mutations were in HWE except for g.67519T>C. The results indicate that these SNPs have a significant association with some body measurements and carcass quality traits (P < 0.05 or P < 0.01). Therefore, STAT3 might have potential effects on production traits in beef cattle populations and could be used for marker-assisted selection.

show abstract

Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Cited by 107 publications

References 40 publications

ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity

ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

Identification of single nucleotide polymorphisms of the signal transducer and activator of transcription 3 gene (STAT3) associated with body measurement and carcass quality traits in beef cattle

Contact Info

Product

Resources

About