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

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

PROVIDER: PRJNA414438 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6177770.fastq.gz	Fastqsanger.gz
	SRR6177780.fastq.gz	Fastqsanger.gz
	SRR6177771.fastq.gz	Fastqsanger.gz
	SRR6177781.fastq.gz	Fastqsanger.gz
	SRR6177772.fastq.gz	Fastqsanger.gz

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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)

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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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2016-05-17 | E-GEOD-80063 | biostudies-arrayexpress

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.

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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)

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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.

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

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

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