| First Author | Rollings CM | Year | 2018 |
| Journal | Sci Signal | Volume | 11 |
| Issue | 526 | PubMed ID | 29666307 |
| Mgi Jnum | J:284392 | Mgi Id | MGI:6381021 |
| Doi | 10.1126/scisignal.aap8112 | Citation | Rollings CM, et al. (2018) Interleukin-2 shapes the cytotoxic T cell proteome and immune environment-sensing programs. Sci Signal 11(526) |
| abstractText | 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. |
