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

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Interleukin-2 (IL-2) and Janus kinases (JAKs) are crucial for effector CD8+ cytotoxic T lymphocyte (CTL) differentiation.
• Understanding the proteomic changes induced by IL-2 and JAK signaling is essential for controlling CTL function.

Purpose of the Study:

• To characterize the proteomic landscape shaped by IL-2 and JAK signaling in CTLs.
• To elucidate how IL-2-JAK1/3 pathways regulate protein synthesis and cellular metabolism.
• To investigate the role of IL-2 in integrating microenvironmental cues, including oxygen sensing, into T cell responses.

Main Methods:

• High-resolution mass spectrometry was employed to analyze the CTL proteome.
• Quantitative proteomic analysis was performed to identify changes in protein abundance.

Main Results:

• IL-2 signaling via JAK1/3 significantly increased the abundance of specific proteins, including cytokines and effector molecules.
• IL-2 signaling maintained protein concentrations vital for cellular metabolic processes and fitness.
• IL-2-JAK1/3 pathways upregulated nutrient transporters, sensors, and oxygen-sensing molecules, enhancing T cell responsiveness to the microenvironment.

Conclusions:

• IL-2 signaling, particularly through JAK1/3, plays a dominant role in enhancing effector CD8+ T cell function by modulating the proteome.
• IL-2 promotes T cell fitness and responsiveness by regulating metabolic proteins and sensing of microenvironmental cues.
• These findings highlight key signaling pathways and transcription factors integrating environmental sensing with T cell differentiation.