Insulin signaling establishes a developmental trajectory of adipose regulatory T cells

Li, Yangyang; Lu, Ying; Lin, Shuhai; Li, Ning; Han, Yichao; Huang, Qing-Guo; Zhao, Yi; Xie, Feng; Guo, Yixian; Deng, Banglin; Tsun, Andy; Du, Juan; Li, Dan; Sun, Joanne; Shi, Guochao; Zheng, Fang; Su, Xiao; Duan, Sheng-Zhong; Zheng, Song Guo; Wang, Gang; Tong, Xuemei; Li, Bin

doi:10.1038/s41590-021-01010-3

Cited by 46 publications

(55 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, PPARγ also regulates the accumulation and function of regulator T cells in the visceral adipose tissue and expression of PPARγ in this unique T cell population is essential for the complete insulin-sensitizing activity of TZDs in obese mice ( Cipolletta et al, 2012 ). PPARγ-axis dependent insulin signaling has also shown to drive state transition between adipose regulatory T cell subsets ( Li et al, 2021 ). PPARγ agonists have also been reported to suppress the progression of atherosclerosis and aortic aneurysmal changes by reducing the expression of TNF-α and other markers of inflammation ( Zinn et al, 2008 ; Motoki et al, 2015 ).…”

Section: Role Of the Inflammasomementioning

confidence: 99%

Salt-Sensitivity of Blood Pressure and Insulin Resistance

et al. 2021

View full text Add to dashboard Cite

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

show abstract

Section: Role Of the Inflammasomementioning

confidence: 99%

Salt-Sensitivity of Blood Pressure and Insulin Resistance

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A new publication also investigated how adipose tissue resident Tregs communicate with adipocytes to affect metabolism and body weight homeostasis [ 22 ]. Li and colleagues published that Tregs recently migrated from the secondary lymphoid tissues to the VAT and subcutaneous adipose tissue (SAT) express the protein CD73, a surface enzyme that converts AMP to adenosine [ 22 ]. Adenosine is used by proximal adipocytes to increase adipocyte thermogenesis [ 23 , 24 ].…”

mentioning

confidence: 99%

“…Adenosine is used by proximal adipocytes to increase adipocyte thermogenesis [ 23 , 24 ]. These recently emigrated Tregs also express low levels of ST2, the high affinity Interleukin-33 (IL-33) receptor [ 22 ]. This study revealed that CD73 + ST2 − Tregs differentiate into mature CD73 − ST2 + adipose tissue resident Tregs through an insulin signaling-driven Hif1α-Med23-PPARγ pathway [ 22 ].…”

mentioning

confidence: 99%

“…These recently emigrated Tregs also express low levels of ST2, the high affinity Interleukin-33 (IL-33) receptor [ 22 ]. This study revealed that CD73 + ST2 − Tregs differentiate into mature CD73 − ST2 + adipose tissue resident Tregs through an insulin signaling-driven Hif1α-Med23-PPARγ pathway [ 22 ]. Indeed, deletion of the insulin receptor on Tregs substantially reduced PPARγ expression in VAT and SAT resident Tregs (PPARγ expression is a hallmark of VAT resident Tregs [ 9 ]) and prevented differentiation of the cells to CD73 − ST2 + Tregs [ 22 ].…”

mentioning

confidence: 99%

“…This study revealed that CD73 + ST2 − Tregs differentiate into mature CD73 − ST2 + adipose tissue resident Tregs through an insulin signaling-driven Hif1α-Med23-PPARγ pathway [ 22 ]. Indeed, deletion of the insulin receptor on Tregs substantially reduced PPARγ expression in VAT and SAT resident Tregs (PPARγ expression is a hallmark of VAT resident Tregs [ 9 ]) and prevented differentiation of the cells to CD73 − ST2 + Tregs [ 22 ]. Similarly, conditional ablation of either Hif1α or Med23 in Tregs also prevented differentiation of adipose tissue resident Tregs to CD73 − ST2 + Tregs [ 22 ].…”

mentioning

confidence: 99%

See 2 more Smart Citations

T Regulatory Cells in the Visceral Adipose Tissues

Fooks¹,

D’Cruz²

2021

Immunometabolism

View full text Add to dashboard Cite

CD4 + Foxp3 + T regulatory cells (Tregs) residing in the visceral adipose tissues (VAT) have profound effects on local and systemic metabolism. Although many of the molecular characteristics of VAT resident Tregs have been identified, how these cells promote metabolic homeostasis is still unclear. Several new publications help to illuminate the molecular mechanisms that underpin VAT resident Treg function and will be discussed here.

show abstract

Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease

et al. 2021

Self Cite

View full text Add to dashboard Cite

Regulatory T (Treg) cells and T helper type 17 (Th17) cells play important roles in adaptive immune responses, antagonizing each other in immune disorders. Th17/Treg balance is critical to maintaining the immune homeostasis of human bodies and is tightly regulated under healthy conditions. The transcription factors that are required for driving Th17 and Treg cell lineages differentiation respectively, RORγt and FOXP3 are tightly regulated under different tissue microenvironment, especially the transcriptional induction, posttranslational modifications, and dynamic enzymatic cofactors binding. The imbalance caused by alteration of the quantity or properties of RORγt + Th17 or FOXP3 + Treg can contribute to inflammatory disorders in humans. Restoring Th17/Treg balance by modifying the enzymatic activities of RORγt and FOXP3 binding partners may be therapeutically applied to treat severe immune disorders. In this review, we focus on the transcriptional and posttranslational regulations of Th17/Treg balance, immune disorders caused by Th17/Treg imbalance, and new therapeutic strategies for restoring immune homeostasis.

show abstract

Insulin signaling establishes a developmental trajectory of adipose regulatory T cells

Cited by 46 publications

References 41 publications

Salt-Sensitivity of Blood Pressure and Insulin Resistance

Salt-Sensitivity of Blood Pressure and Insulin Resistance

T Regulatory Cells in the Visceral Adipose Tissues

Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease

Contact Info

Product

Resources

About