Transcriptional programing of T cell metabolism by STAT family transcription factors

Area of Science:

• Immunology
• Cellular Metabolism
• Molecular Signaling

Background:

• T cells dynamically adjust their metabolism to suit diverse functional states and environments.
• Cytokines are key regulators of T cell metabolism, traditionally studied through PI3K-AKT, mTOR, and ERK-MAPK pathways.
• Emerging evidence highlights the critical role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in T cell metabolic control.

Purpose of the Study:

• To review and synthesize current understanding of how JAK-STAT signaling influences T cell metabolism.
• To focus on JAK-STAT's role in metabolic adaptations across various T cell subsets, including naïve, effector, regulatory, memory, and resident-memory cells.
• To elucidate the direct and indirect mechanisms by which JAK-STAT signaling impacts T cell metabolic pathways.

Main Methods:

• Literature review and synthesis of existing research on JAK-STAT signaling and T cell metabolism.
• Analysis of direct regulatory mechanisms involving STATs binding to metabolism-related genes.
• Examination of indirect regulatory mechanisms, including STATs' influence on cytokine receptors and transcription factors.

Main Results:

• JAK-STAT signaling exerts both direct and indirect control over T cell metabolism.
• Direct effects include STATs regulating the expression of genes involved in lipid, amino acid, and nucleotide synthesis.
• Indirect effects involve STATs modulating upstream factors like cytokine receptors and other transcription factors, alongside non-canonical activities.

Conclusions:

• JAK-STAT signaling is a central regulator of T cell metabolic reprogramming.
• It influences anabolic processes (synthesis) and catabolic processes (energy production) such as glycolysis, glutaminolysis, and oxidative phosphorylation.
• JAK-STAT acts as a key integration point, ensuring T cell metabolism aligns with their functional demands.