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LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity [HT_MG-430_PM]

ABSTRACT: LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity [HT_MG-430_PM]

PROVIDER: PRJNA527819 | ENA |

REPOSITORIES: ENA

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LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity

Project description:LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity

| PRJNA527815 | ENA

LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity [MoGene-2_0-st]

Project description:LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity [MoGene-2_0-st]

| PRJNA527817 | ENA

LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity.

Project description:Dendritic cells (DCs) play a pivotal role in priming adaptive immunity. However, the involvement of DCs in controlling excessive and deleterious T cell responses remains poorly defined. Moreover, the metabolic dependence and regulation of DC function are unclear. Here we show that LKB1 signaling in DCs functions as a brake to restrain excessive tumor-promoting regulatory T cell (Treg) and Th17 cell responses, thereby promoting protective anti-tumor immunity and maintaining proper immune homeostasis. LKB1 deficiency results in dysregulated metabolism and mTOR activation of DCs. Loss of LKB1 also leads to aberrant DC maturation and production of cytokines and immunoregulatory molecules. Blocking mTOR signaling in LKB1-deficient DCs partially rectifies the abnormal phenotypes of DC activation and Treg expansion, whereas uncontrolled Th17 responses depend upon IL-6-STAT3 signaling. By coordinating metabolic and immune quiescence of DCs, LKB1 acts as a crucial signaling hub in DCs to enforce protective anti-tumor immunity and normal immune homeostasis.

| S-EPMC6796952 | biostudies-literature

LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity [HT_MG-430_PM]

Project description:Loss of LKB1 leads to aberrant DC maturation and production of cytokines and immunoregulatory molecules. DCs (n = 7 per genotype) were isolated from the spleen, and CD25+CD4+ Tregs (n = 4 for WT, n = 3 for LKB1ΔDC mice) were isolated from the spleen and peripheral lymph nodes of WT and LKB1ΔDC mice.

2019-04-16 | GSE128474 | GEO

LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity [MoGene-2_0-st]

2019-04-16 | GSE128473 | GEO

LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-04-16 | GSE128475 | GEO

LKB1 expressed in dendritic cells governs the development and expansion of thymus-derived regulatory T cells

Project description:Liver Kinase B1 (LKB1) plays a key role in cellular metabolism by controlling AMPK activation. However, its function in dendritic cell (DC) biology has not been addressed. Here, we find that LKB1 functions as a critical brake on DC immunogenicity, and when lost, leads to reduced mitochondrial fitness and increased maturation, migration, and T cell priming of peripheral DCs. Concurrently, loss of LKB1 in DCs enhances their capacity to promote output of regulatory T cells (Tregs) from the thymus, which dominates the outcome of peripheral immune responses, as suggested by increased resistance to asthma and higher susceptibility to cancer in CD11cΔLKB1 mice. Mechanistically, we find that loss of LKB1 specifically primes thymic CD11b+ DCs to facilitate thymic Treg development and expansion, which is independent from AMPK signalling, but dependent on mTOR and enhanced phospholipase C β1-driven CD86 expression. Together, our results identify LKB1 as a critical regulator of DC-driven effector T cell and Treg responses both in the periphery and the thymus.

2020-05-07 | GSE149941 | GEO

LKB1 prevents ILC2 exhaustion and lung cancer metastasis

Project description:Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses involved in anti-helminth immunity, allergic inflammation, and metabolic homeostasis. Recently, they have emerged as key players in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations is associated with a variety of human cancers, but the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that LKB1 is required for mature ILC2 survival. Ablation of LKB1 in ILC2s results in impaired proliferation and a marked decrease in type 2 cytokine production upon activation, accompanied with the expression of exhaustion signature genes and reduced cellular metabolism, which promote the development of lung melanoma metastasis. In addition, LKB1 deficiency leads to a marked increase of programmed cell death protein-1 (PD-1) expression in ILC2s through activation of nuclear factor of activated T cells (NFAT) pathway. Blockade of PD-1 can restore type 2 cytokine production in LKB1-deficient ILC2 and reverse its exhaustion state, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 retrains ILC2 exhaustion state to maintain immune homeostasis and their antitumor immunity.

2024-05-21 | GSE209588 | GEO

LKB1 regulates ILC3 postnatal development and effector function through metabolic programming

Project description:Group 3 Innate Lymphoid Cells (ILC3s) is important for maintaining intestinal homeostasis and host defense. Emerging studies have shown that metabolic regulation plays a crucial role in regulating ILC3 activation and function. However, the role of Liver Kinase B1 (LKB1), key metabolic regulator, in regulating ILC3 function and intestinal immunity remains poorly understood. In this study, we show that LKB1 is essential for ILC3 postnatal development, effector function, and intestinal immunity. Ablation of LKB1 in ILC3s results in reduced cell number due to increased apoptosis and reduced proliferation, which occurs at 2 -3 weeks after birth. In addition, LKB1 deletion leads to diminished IL-22 production and less protection against C.rodentium infection. Mechanistically, LKB1 deficiency led to impaired mitochondrial metabolism, as indicated by reduced glycolysis and oxidative phosphorylation and less mitochondrial mass. Together, our data demonstrate that LKB1 promotes ILC3 postnatal development and effector function to maintain intestinal immune homeostasis.

2025-06-25 | GSE284792 | GEO

PROX1 Orchestrates Tumor Metabolic Plasticity by Integrating LKB1-AMPK Signaling with BCAA Catabolism

Project description:PROX1 Orchestrates Tumor Metabolic Plasticity by Integrating LKB1-AMPK Signaling with BCAA Catabolism

| PRJNA884334 | ENA