Dataset Information

Blocking ERK activity has a selective but critical impact on activating T cells

ABSTRACT: The mitogen activated kinases ERK1/2 are activated by antigen receptor engagement and control T cell differentiation. We have used mass spectrometry to explore how ERK1/2 control antigen receptor driven cell growth and proteome restructuring in CD8 T cells. Quantitative analysis of >8000 proteins provides new understanding of the highly selective role of ERK1/2 in controlling T cell protein systems. The data reveal that ERK signalling is not a dominant regulator of the metabolic and biosynthetic programs that drive T cell growth. Rather, the dominant function of ERK1/2 is to control the repertoire of transcription factors, cytokines and cytokine receptors expressed by activated T cells. This study provides a comprehensive map of how T cell phenotypes are selectively shaped by ERK1/2 and reveals that ERK1/2 controls the transcriptional reprogramming of activated T cells that is pivotal for T cell differentiation and acquisition of effector function.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell, Lymph Node

SUBMITTER: Andrew Howden

LAB HEAD: Professor Doree Cantrell

PROVIDER: PXD023256 | Pride | 2020-12-23

REPOSITORIES: Pride

ACCESS DATA

Similar Datasets

Project description:Objectives: Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Methods: Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. Results: PNLA reduced percentage of monocytes expressing cytokines: TNF-a by 23% (p=0.048), IL-6 by 25% (p=0.011), IL-1B by 23% (p=0.050), IL-8 by 20% (p=0.066). Pathway analysis identified upstream activation of peroxisomes proliferator-activated receptors (PPARs), sirtuin3, and let7miRNA, KLF15 which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-a, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p=9.14E-09) and mitochondrial dysfunction (p=4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p=8.89E-06) which interfere with the pathophysiologic process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and Acetyl-CoA Acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. Conclusion: PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

Dataset Information

Blocking ERK activity has a selective but critical impact on activating T cells

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure