2017
DOI: 10.1038/ncomms15876
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Lkb1 maintains Treg cell lineage identity

Abstract: Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific de… Show more

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Cited by 71 publications
(77 citation statements)
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References 55 publications
(103 reference statements)
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“…To investigate the role of LKB1 in the homeostasis and suppressive activity of T reg cells, we crossed mice carrying loxP-flanked STK11 alleles (LKB1 fl/fl ) with Foxp3 YFP-Cre (referred to as Foxp3-Cre) mice (Rubtsov et al, 2008) to generate progeny in which LKB1 alleles are conditionally deleted in T reg cells, but not in other T cells (hereafter referred to as LKB1 fl/fl Foxp3-Cre mice; LKB1 +/+ Foxp3-Cre mice were used as control) ( Figure S1A). Consistent with previous reports (He et al, 2017;Wu et al, 2017;Yang et al, 2017), LKB1 fl/fl Foxp3-Cre mice developed severe systemic inflammatory diseases ( Figure S1). Hematological analysis showed red blood cells, hemoglobin, hematocrit, and platelets in circulation were lower in the LKB1 fl/fl Foxp3-Cre mice than in the control mice, indicating severe inflammatory conditions in the former mice ( Figure S1F).…”
Section: Resultssupporting
confidence: 92%
“…To investigate the role of LKB1 in the homeostasis and suppressive activity of T reg cells, we crossed mice carrying loxP-flanked STK11 alleles (LKB1 fl/fl ) with Foxp3 YFP-Cre (referred to as Foxp3-Cre) mice (Rubtsov et al, 2008) to generate progeny in which LKB1 alleles are conditionally deleted in T reg cells, but not in other T cells (hereafter referred to as LKB1 fl/fl Foxp3-Cre mice; LKB1 +/+ Foxp3-Cre mice were used as control) ( Figure S1A). Consistent with previous reports (He et al, 2017;Wu et al, 2017;Yang et al, 2017), LKB1 fl/fl Foxp3-Cre mice developed severe systemic inflammatory diseases ( Figure S1). Hematological analysis showed red blood cells, hemoglobin, hematocrit, and platelets in circulation were lower in the LKB1 fl/fl Foxp3-Cre mice than in the control mice, indicating severe inflammatory conditions in the former mice ( Figure S1F).…”
Section: Resultssupporting
confidence: 92%
“…However, in the hematopoietic system, LKB1 appears to sustain metabolic homeostasis through downstream ARKs largely independent of AMPK . Similarly, LKB1 functions independently from AMPK to maintain metabolism in regulatory T cells, and rather acts through the salt inducible kinases (SIKs) or MAP/microtubule affinity‐regulating kinases (both belonging to the ARKs) . In the liver, LKB1 suppresses gluconeogenesis in hepatocytes also through the SIKs, independent from AMPK .…”
Section: The Lkb1‐ampk and Mtorc1 Signaling Hubs As Central Regulatormentioning
confidence: 99%
“…However, these data involved pan‐inhibition of their relevant enzymes and so did not reflect the effects of modulating their numerous isoforms. This is important as divergence in the inhibition of different isoforms and their effects on Treg function is known . The authors also used an HDAC9 KO murine model to demonstrate a boost to the quantity of Treg cells and their function.…”
Section: Heterogeneity Of Treg Cellsmentioning
confidence: 99%
“…This is important as divergence in the inhibition of different isoforms and their effects on Treg function is known. 61,62 The authors also used an HDAC9 KO murine model to demonstrate a boost to the quantity of Treg cells and their function. Similar effects have also been demonstrated in the studies focussing on inhibition of HDAC3/10/11 either pharmacologically or via enzyme KO or Tregspecific enzyme KO.…”
Section: How Important Is Foxp3 Expression In Treg Cells?mentioning
confidence: 99%