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Critical role for very-long chain sphingolipids in invariant natural killer T cell development and homeostasis

ABSTRACT: Critical role for very-long chain sphingolipids in invariant natural killer T cell development and homeostasis

PROVIDER: PRJNA412033 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6069501.fastq.gz	Fastqsanger.gz
	SRR6069502.fastq.gz	Fastqsanger.gz
	SRR6069503.fastq.gz	Fastqsanger.gz
	SRR6069504.fastq.gz	Fastqsanger.gz
	SRR6069495.fastq.gz	Fastqsanger.gz

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Critical role for very-long chain sphingolipids in invariant natural killer T cell development and homeostasis

Project description:The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2 (CerS2) null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of iNKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for iNKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in iNKT cell physiology.

2017-10-15 | GSE104205 | GEO

Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

Project description:The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of iNKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for iNKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in iNKT cell physiology.

| S-EPMC5672022 | biostudies-literature

Gene Regulation by Histone Deacetylase 7 During Invariant Natural Killer T Cell Development

Project description:We have found that the signal-dependent chromatin modulator Histone Deacetylase 7 interacts with and corepresses the signature transcription factor of invariant natural Killer T (iNKT) cells, ZBTB16. This study was designed to determine the global effect on transcription of a gain-of-function mutant of HDAC7 during iNKT cell development and function. Va14/Ja18 T cell receptor transgenic thymocytes and splenocytes, which develop preferentially into iNKT cells, were profiled by RNA-seq with and without expression of a gain-of-functon HDAC7 transgene (HDAC7dP)

2018-05-08 | GSE105026 | GEO

Single-cell RNAseq profiling of mouse invariant NKT thymocytes

Project description:Total invariant Natural Killer T cells were purified from mouse thymi (pool of 4 mice) of Fhl2+/+ or Fhl2-/- mice (5 week-old)

2020-09-08 | GSE141895 | GEO

Gene Regulation by Histone Deacetylase 7 During Invariant Natural Killer T Cell Development

Project description:Gene Regulation by Histone Deacetylase 7 During Invariant Natural Killer T Cell Development

| PRJNA414438 | ENA

Mitochondrial Metabolism is Essential for Invariant Natural Killer T Cell Development and Function

Project description:Mitochondrial Metabolism is Essential for Invariant Natural Killer T Cell Development and Function

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Dual regulatory role of invariant natural killer T cells in the development and progression of hepatocellular carcinoma

Project description:Our project aims to examine the role of Invariant Natural Killer T cells (iNKT) in Hepatocellular Carcinoma (HCC) which is not known. HCC is a leading cause of death and accounts for ~80% of cases of liver cancer worldwide. Because there are no biomarkers that allow the early diagnosis, HCC is diagnosed at late stages when the tumor is developed enough and is resistant to chemotherapy. The liver is characterized by an immunosuppressive environment and due to this environment, liver is prone to HCC development. Once HCC is developed, the function of immune cells that fight the tumor such as dendritic cells, natural killer cells, helper and cytotoxic T cells is suppressed while the function of regulatory T cells and myeloid- derived suppressor cells is enhanced. However, the role of Natural Killer T cells (NKT) is not known. NKT cells is a population of the immune system which is largely enriched in the liver, which recognize lipid antigens by CD1d molecule and can rapidly produce large amounts of various cytokines to enhance the function of other immune populations. Here, we investgated the role of NKT cell in chemical-induced HCC that recapitulates the development of human HCC usiing genetic models that lack or overproduce NKT cells.

2025-08-11 | GSE279202 | GEO

Mitochondrial Metabolism is Essential for Invariant Natural Killer T Cell Development and Function

Project description:Conventional T cell fate and function are determined by coordination between cellular signaling and metabolism. Invariant natural killer T (iNKT) cells are a subset of “innate-like” pre-activated T cells whose dependence on mitochondrial metabolism remains elusive. Here, we showed that mature iNKT cells have reduced mitochondrial respiratory reserve and iNKT cell development was highly sensitive to perturbation of mitochondrial function. Mice with T cell-specific ablation of Rieske Iron-Sulphur protein (T-Uqcrfs1-/-), an essential subunit of mitochondrial complex III, had a dramatic reduction of iNKT cells in the thymus and periphery, but minimal effects on conventional T cell development. Residual iNKT cells in T-Uqcrfs1-/- mice retained ability to proliferate but exhibited increased apoptosis, decreased TCR signaling and impaired responses to TCR and IL-15 stimulation. Furthermore, knocking down RISP in mature iNKT cells diminished their cytokine production, correlating with reduced NFATC2 activity. Collectively, our data demonstrate a critical role for mitochondrial metabolism in iNKT cell development and activation outside of supporting bioenergetic demands.

2021-03-12 | GSE157283 | GEO

Very long-chain ceramides in skeletal muscle associate with systemic insulin resistance independent of obesity

Project description:Lipids are bioactive signaling molecules implicated in tissue-specific and whole-body insulin resistance, with ceramides and diacylglycerols (DAGs) as prominent species. Their precise roles remain unclear. Here, we leverage natural genetic variation in 399 male Diversity Outbred Australia (DOz) mice fed chow or a high-fat diet to examine the relationship between muscle lipids and insulin sensitivity. Fat mass was significantly associated with 55% of muscle lipid features and whole-body insulin sensitivity, with DAGs enriched in this association. To disentangle adiposity and muscle lipid contributions, we used: (1) linear models correcting lipid features for fat mass, and (2) insulin sensitivity quartiles within adiposity bins. Both approaches identified very long-chain ceramides, not DAGs, as linked to insulin resistance. RNA sequencing and proteomics from the same muscles associated these ceramides with cellular stress, mitochondrial dysfunction, and protein synthesis regulation. Meanwhile, DAGs correlated with leptin gene expression, suggesting an adipocyte, rather than myocyte, origin. These findings highlight very long-chain ceramides as key muscle lipids associated with insulin resistance, independent of adiposity.

2025-08-06 | GSE290031 | GEO

Gene expression profile of canine Chimeric Antigen Receptor (CAR) Engineered invariant Natural Killer T (iNKT) cells

Project description:Gene expression profile of canine Chimeric Antigen Receptor (CAR) Engineered invariant Natural Killer T (iNKT) cells

| PRJNA954687 | ENA