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

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

PROVIDER: PRJNA660761 | ENA |

REPOSITORIES: ENA

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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

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

Mitochondrial metabolism is essential for invariant natural killer T cell development and function.

Project description: Not available

| S-EPMC8020658 | biostudies-literature

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

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

Expression profiling of Natural killer B cells

Project description:Investigation of global gene expression levels between B cells, Natural killer cells and Natural killer B cells Gene expression profiling using sorted B cells, Natural killer cells and Natural killer B cells from WT mouse spleen. Total RNA extracted from WT cells were quantified by the NanoDrop ND-1000 and RNA integrity was assessed by standard denaturing agarose gel electrophoresis. The sample preparation and microarray hybridization were performed based on the NimbleGenâs standard protocols.

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

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

Expression profiling of Natural killer B cells

Project description:Investigation of global gene expression levels between B cells, Natural killer cells and Natural killer B cells

2016-05-17 | GSE80063 | GEO

Transcription profiling of neonatal and adult mouse natural killer cells

Project description:Comparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.

2005-10-01 | E-MEXP-354 | biostudies-arrayexpress

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

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

| PRJNA412033 | ENA