De novo fatty acid synthesis in invariant NKT cells is critical for the development of airway hyperresponsiveness
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ABSTRACT:
PROVIDER: PRJNA847543 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19594959_1.fastq.gz | Fastqsanger.gz | |||
| SRR19594959_2.fastq.gz | Fastqsanger.gz | |||
| SRR19594960_1.fastq.gz | Fastqsanger.gz | |||
| SRR19594960_2.fastq.gz | Fastqsanger.gz |
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Project description:Allergic responses in airway against house dust mites (HDMs) depend on lipid metabolism. However, whether the state of lipid metabolism in iNKT cells serves as a critical mechanism to impact development of allergic asthma remains elusive. Here, we showed that acetyl-CoA-Carboxylase 1 (ACC1), a key enzyme for fatty acid synthesis, was highly expressed in iNKT cells from asthmatic lungs. In ovalbumin (OVA)- and HDM-induced allergic asthma models, Cd4-CreAcc1fl/fl mice exhibited impaired homeostasis of iNKT cells and failed to develop AHR. ACC1-deficient iNKT cells reduced intracellular lipid concentration and expression of fatty acid binding proteins (FABPs) and peroxisome proliferator-activated receptor-gamma (PPAR-γ), whereas these cells were increased in glycolytic capacity. Moreover, ACC1-FABP-PPAR-γ axis regulated cell death of ACC1-deficient iNKT cells. Adoptive transfer of wild type (WT) iNKT cells restored AHR in Jɑ18 knockout mice in OVA or HDM-induced asthma models, whereas that of ACC1-deficient iNKT cells did not, indicating that fatty acid synthesis in iNKT cells is one of main contributors to the development of AHR. Our finding demonstrate fatty acid metabolism in iNKT cells is critical contributor for the development of AHR and airway inflammation in asthma.
2022-06-15 | GSE205761 | GEO
Project description:Invariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in iNKT cells is very limited. It is also not clear whether such metabolic regulation of iNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediated de novo fatty-acid synthesis is required for the survival of iNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lung iNKT cells from WT mice that were developing asthma. Cd4-Cre::Acc1fl/fl mice failed to develop OVA-induced and HDM-induced asthma. Moreover, iNKT cell-deficient mice that were reconstituted with ACC1-deficient iNKT cells failed to develop asthma, unlike when WT iNKT cells were transferred. ACC1 deficiency in iNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR)γ, but increased glycolytic capacity that promoted iNKT-cell death. Furthermore, circulating iNKT cells from allergic-asthma patients expressed higher ACC1 and PPARG levels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus, de novo fatty-acid synthesis prevents iNKT-cell death via an ACC1-FABP-PPARγ axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.
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Project description:Aim of the experiment was to characterize the gene activation profile<br><br>induced within immature myeloid DCs by cell-cell contact with activated<br><br>invariant NKT cells under steady-state conditions.
2010-10-08 | E-MEXP-2938 | biostudies-arrayexpress
Project description:Single-cell RNAseq profiling of mouse invariant NKT thymocytes
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Project description:Invariant Natural killer T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small non-coding RNAs that regulate gene expression posttranscriptionally and play key role in the control of cellular differentiation programs. We identified a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes. In this experiment we compared microRNAs of NKT cells versus those of conventional T lymphocytes, both extracted from wild type mouse thymus. To produce the populations we enriched mature thymocytes and then sorted NKT cells and conventional T cells (from one sorting we obtain one â??NKTâ?? sample and one â??Tâ?? sample). We performed the experiment in triplicate; the sample NKT 1 was sorted the same day of the sample T 1, NKT 2 with T 2, NKT 3 with T 3. We used a common reference approach for the 6 samples; as a common reference we produced RNA from total thymocytes, without the enrichment for mature cells and without the sorting; we pooled thymocytes derived from all the thymi used in the study. The aim of the experiment was to demonstrate that NKT cells have a microRNA profile different from that of conventional T cells.
2010-04-09 | E-GEOD-15925 | biostudies-arrayexpress
Project description:We compared splenic Va14i NKT cells from C57BL/6 control mice and from mice injected 4 weeks earlier intravenously with 4ug/mouse of the iNKT cell antigen alpha-galactosylceramide (aGalCer). These mice were either left unstimulated or were stimulated with 1ug/mouse aGalCer i.v.. All mice were female and 8 weeks of age at the beginning of the experiment. Va14i NKT cells were enriched via magnetic selection and cell sorted for TCRb+ CD1d/aGalCer-tetramer+. Total RNA were prepared using a Qiagen RNeasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD. Group 1 (Ctr_unstim) = iNKT cells from C57BL/6 control mice and left unstimulated / Group 2 (Ctr_stim) = iNKT cells from C57BL/6 control mice and injected 1h before purification with 1ug aGalCer i.v. / Group 3 (Pre_unstim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and left unstimulated / Group 4 (Pre_stim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and injected 1h before purification with 1ug aGalCer i.v. / Sample were prepared in duplicates in two independent experiments.
2014-07-25 | E-GEOD-47959 | biostudies-arrayexpress
Project description:We compared splenic Va14i NKT cells from C57BL/6 control mice and from mice injected 4 weeks earlier intravenously with 4ug/mouse of the iNKT cell antigen alpha-galactosylceramide (aGalCer). These mice were either left unstimulated or were stimulated with 1ug/mouse aGalCer i.v.. All mice were female and 8 weeks of age at the beginning of the experiment. Va14i NKT cells were enriched via magnetic selection and cell sorted for TCRb+ CD1d/aGalCer-tetramer+. Total RNA were prepared using a Qiagen RNeasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD.
2014-07-25 | GSE47959 | GEO
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
Project description:Semi-invariant natural killer T (NKT) cells are thymus-derived innate lymphocytes that modulate microbial and tumour immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learnt regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-xL expression. Additionally, IL-15 regulated thymic developmental stage 2 (ST2) to ST3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic ST3 NKT cells. The loss of IL15-dependent T-bet expression resulted in poor expression of IFN-γ and several NK cell receptors in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-xL, and effector differentiation, which is regulated by T-bet. Gene expression was measured in NKT cells sorted from pooled thymi of wild-type (3 replicates) or IL-15 deficient (2 replicates) mice.
2011-12-08 | E-GEOD-32568 | biostudies-arrayexpress
Project description:Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70
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