Dataset Information

Impact of Age and Sex on Plasma Proteome Changes in Mice upon Radiation Exposure

ABSTRACT: The aim of this project is to assess the impact that age and sex have as parameters for biomarker discovery in radiation research using high-throughput proteomics.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Egor Vorontsov

LAB HEAD: Eva Forssell-Aronsson

PROVIDER: PXD015859 | Pride | 2022-05-10

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2211_3109_Plasma_Labeling_Scheme.pdf	Pdf
	2211_Plasma_2nd-attempt_TMT-SET1_HighpH-AKTA-All-frs_0mc_160311.msf	Msf
	2211_Plasma_2nd-attempt_TMT-SET2_HighpH-AKTA-All-frs_0mc_160311.msf	Msf
	3109_Plasma2_Set5_Fusion_190503_08_27.msf	Msf
	3109_Plasma2_Set6_Fusion_190503_33_52.msf	Msf

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Project description:Treatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor post-infusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK cell functions following cytokine withdrawal to model post-infusion performance. In contrasts to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided functional advantages. Genome-wide analysis of cytosolic and polysome-associated mRNA revealed cytokine dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mTOR signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced functional advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15 stimulated NK cells was also observed using a clinically applicable protocol for NK cell expansion. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK cell cancer therapy. Freshly isolated NK cells from 6 donors were activated with IL-2 or IL-15 for 48 hours, followed by cytokine withdrawal for 24 hours, resulting in four RNA samples per donor. From each sample, both the cytosolic as well as the polysomal fraction were collected. Donor 3 contains activation and post withdrawal data from two different donors due to poor RNA-quality obtained for some samples which did not allow for processing of the complete set of 6 donors (resulting in a total of 40 samples).

Dataset Information

Impact of Age and Sex on Plasma Proteome Changes in Mice upon Radiation Exposure

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