The Bone Marrow Protects and Optimizes Immunological Memory during Dietary Restriction
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ABSTRACT:
PROVIDER: PRJNA510644 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8350380.fastq.gz | Fastqsanger.gz | |||
| SRR8350390_1.fastq.gz | Fastqsanger.gz | |||
| SRR8350390_2.fastq.gz | Fastqsanger.gz | |||
| SRR8350381.fastq.gz | Fastqsanger.gz | |||
| SRR8350391_1.fastq.gz | Fastqsanger.gz |
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Project description:Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This response was coordinated by glucocorticoids and associated with a profound remodeling of the BM compartment, which included an increase in T cell homing factors, erythropoiesis, and adipogenesis. Adipocytes and CXCR4-CXCL12 and S1P-S1P1R interactions contributed to enhanced T cell accumulation in BM during DR. Memory T cell homing to BM during DR was associated with enhanced protection against infections and tumors. Together, this work uncovers a fundamental host strategy to sustain and optimize immunological memory during nutritional challenges that involved a temporal and spatial reorganization of the memory pool within ‘‘safe haven’’ compartments.
2019-08-22 | GSE124063 | GEO
Project description:Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This response was coordinated by glucocorticoids and associated with a profound remodeling of the BM compartment, which included an increase in T cell homing factors, erythropoiesis, and adipogenesis. Adipocytes, as well as CXCR4-CXCL12 and S1P-S1P1R interactions, contributed to enhanced T cell accumulation in BM during DR. Memory T cell homing to BM during DR was associated with enhanced protection against infections and tumors. Together, this work uncovers a fundamental host strategy to sustain and optimize immunological memory during nutritional challenges that involved a temporal and spatial reorganization of the memory pool within "safe haven" compartments.
| S-EPMC6818271 | biostudies-literature
Project description:Dietary restriction (DR) is the most powerful natural means to extend lifespan. Here we obtain temporally resolved transcriptomes during calorie restriction and intermittent fasting in Caenorhabditis elegans, and find that early and late responses involve metabolism and cell cycle/DNA damage, respectively.
2016-01-22 | GSE77110 | GEO
Project description:Dietary protein dilution (DPD) promotes metabolic remodelling and health but the precise nutritional components driving this response remain elusive. Here we demonstrate that dietary amino acids (AA) are sufficient and necessary to drive the response to DPD. In particular, the restriction of dietary essential AA (EAA) supply, but not non-EAA, drives the systemic metabolic response to total AA deprivation. Furthermore, systemic deprivation of Thr and Trp, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Thr is also potentially limiting in low-protein diet fed humans, and dietary Thr restriction (DTR) retarded the development of obesity-associated metabolic dysfunction in mice. Liver-derived fibroblast growth factor 21 was required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of Thr biosynthetic capacity reversed the systemic response to DTR. Taken together, our studies demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.
2020-06-15 | PXD018205 | Pride
Project description:Dietary restriction is a nutritional intervention that consistently increases life span in animals. To identify alternative, more acceptable nutritional regimes that nevertheless extend life span, we used the fruit fly Drosophila melanogaster as a model. We tested if weekly recurring nutritional regimes composed of phases of ad libitum feeding and dietary restriction can increase life span. Short periods of dietary restriction (up to 2 days) followed by longer ad libitum phases increased life span only marginally, whereas regimes comprising longer contiguous periods (3 days and more) became clearly positive, reaching similar life span extensions as those seen if dietary restriction was applied persistently. Female flies were substantially more responsive to these interventions than males. The finding that a minimal period of 3-4 days of dietary restriction is required to induce robust life span extensions was mirrored by the observation that substantial physiological and transcriptional changes occurred in a similar temporal pattern. Moreover, these dietary restriction induced changes were also detectable after switching to ad libitum feeding. Among the physiological changes induced by these phases of dietary restriction, a reduced metabolic rate and a substantial and long-lasting reduction in insulin signaling were most compelling. Age associated molecular signatures comprising mechanisms that reduce insulin signaling showed up after longer periods of dietary restriction in the fly’s fat body, thus showing how molecular alterations transduce into life span related physiological changes.
2017-12-21 | GSE95349 | GEO
Project description:Intestinal cancers are highly responsive to their nutrient environment. However, previous studies integrating nutrition into the network of cancer progression are largely inconsistent. We therefore investigated the effects of dietary restriction, which is the most consistently found beneficial nutritional intervention, on the development of intestinal stem cell tumors in a Drosophila melanogaster model. Submission to dietary restriction led to a decline in tumor mass and a morphological as well as functional rehabilitation of the intestine. Nevertheless, flies submitted to dietary restriction exhibited a drastically reduced lifespan due to substantial loss of body mass. To circumvent these destructive consequences, we applied a nutritional regimen consisting of alternating phases of dietary restriction and a fully nutritious diet. Strikingly, the recurrent diet reduced tumor mass and reinstated gut functionality to the same extend as continuous dietary restriction, while restoring the lifespan of tumor-bearing flies back to the level of healthy controls.
2021-07-05 | GSE134485 | GEO
Project description:Dietary restriction regulates microRNAs in longevity regulons
| PRJNA556814 | ENA
Project description:mRNA expression profiling of genes regulated by dietary restriction and SEK-1.
2016-12-27 | GSE92902 | GEO
Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level.
2011-07-21 | GSE26724 | GEO
Project description:Aims/hypothesis: Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of the metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to identify whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. Methods: We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. A total of 21 individuals diagnosed with the metabolic syndrome was randomly assigned for caloric restriction (CR; n = 11, mean age 49 ± 8.5 years, female 63%; diet of 5,941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, mean age 51.6 ± 8.9 years, female 50%; diet of 8,409 ± 2,360 KJ per day) and followed for 27 days. Results: Like CR, PR promoted weight loss (-6.6%, P= 0.0041) due to reduction in adiposity (-9.9%, P= 0.0007), associated with reductions in blood glucose (-52.7%, P= 0.0002), lipid levels (cholesterol, -35.4%, P= 0.0010; triglycerides, -39.5% P= 0.0022) and blood pressure (systolic, -37.7 P< 0.0001; diastolic, -73.2% P< 0.0001). PR resulted in enrichment of metabolic pathways related to the immune system such as B cell proliferation, lymphocyte proliferation and leukocyte proliferation in subcutaneous adipose tissue. Hence, a reduction in calorie intake or changes in the gut microbiome are not necessary to confer the metabolic benefits of DR. Instead, a reduction in protein intake with a mild increase in carbohydrate intake to maintain the isocaloric balance of the diet is sufficient to improve metabolic control. Conclusions/interpretation: Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has greater potential to be used as adjuvant therapy for people with the metabolic syndrome.
2022-06-20 | GSE192587 | GEO