Interleukin-2 shapes the cytotoxic T cell proteome and immune environment-sensing programs.
Sci Signal
; 11(526)2018 04 17.
Article
de En
| MEDLINE
| ID: mdl-29666307
ABSTRACT
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 and effector molecules in T cells. Moreover, IL-2 maintained the concentration of proteins that support core metabolic processes essential for cellular fitness. One fundamental insight was the dominant role for IL-2 in stimulating effector T cells to detect microenvironmental cues. IL-2-JAK1/3 signaling pathways thus increased the abundance of nutrient transporters, nutrient sensors, and critical oxygen-sensing molecules. These data provide key insights into how IL-2 promotes T cell function and highlight signaling mechanisms and transcription factors that integrate oxygen sensing to transcriptional control of CD8+ T cell differentiation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes T cytotoxiques
/
Interleukine-2
/
Lymphocytes T CD8/
/
Protéome
/
Protéomique
/
Microenvironnement cellulaire
Limites:
Animals
Langue:
En
Journal:
Sci Signal
Sujet du journal:
CIENCIA
/
FISIOLOGIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Royaume-Uni