Proteomics

Dataset Information

45

Interleukin-2 shapes the cytotoxic T cell proteome and immune-environment sensing


ABSTRACT: Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to control the differentiation of effector CD8+ cytotoxic T cells (CTL). Using high-resolution mass spectrometry, we have generated an in-depth characterisation of how IL-2 and JAKs configure the CTL proteome to control CTL function. We found that IL-2-JAK1/3 signaling selectively regulated the abundance of a key subset of proteins influencing the accumulation of critical cytokines and effector molecules in T cells. Moreover, IL-2 controlled the concentration of proteins that support core metabolic processes essential for cellular fitness. One fundamental insight was the dominant role for IL-2 in controlling how effector T cells respond to their microenvironment. IL-2-JAK1/3 signaling pathways thus controlled the abundance of nutrient transporters, nutrient sensors and critical oxygen sensing molecules. The data provide key insights of how IL-2 controls T cell function and highlight signaling mechanisms and transcription factors that link oxygen sensing to transcriptional control of CD8+ T cell differentiation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus musculus  

TISSUE(S): Primary Cell

DISEASE(S): Not Available

SUBMITTER: Sarah Ross  

LAB HEAD: Doreen Ann Cantrell

PROVIDER: PXD008112 | Pride | 2018-04-17

REPOSITORIES: pride

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Publications

Interleukin-2 shapes the cytotoxic T cell proteome and immune environment-sensing programs.

Rollings Christina M CM   Sinclair Linda V LV   Brady Hugh J M HJM   Cantrell Doreen A DA   Ross Sarah H SH  

Science signaling 20180417 526


Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to promote the differentiation of effector CD8+ cytotoxic T lymphocytes (CTLs). Using high-resolution mass spectrometry, we generated an in-depth characterization of how IL-2 and JAKs configure the CTL proteome to control CTL function. We found that IL-2 signaling through JAK1 and JAK3 (JAK1/3) increased the abundance of a key subset of proteins to induce the accumulation of critical cytokines a  ...[more]

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