Wnt activation promotes memory T cell polyfunctionality via epigenetic regulator PRMT1

Area of Science:

• Immunology
• Epigenetics
• Molecular Biology

Background:

• T cell polyfunctionality is crucial for immunity but its regulation is poorly understood.
• Canonical Wnt agonists were investigated for their role in T cell responses.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying T cell polyfunctionality.
• To investigate the role of Wnt signaling and PRMT1 in T cell function.

Main Methods:

• Human memory CD8+ T cells were treated with Wnt agonists.
• Gene expression, epigenetic modifications (H4R3me2a), and cytokine production (IL-2) were analyzed.
• In vivo studies and analysis of patient samples (CMV D+/R- lung transplant) were performed.

Main Results:

• Wnt agonists promoted polyfunctional CD8+ T cells with persistent effects, suggesting epigenetic regulation.
• Wnt activation upregulated PRMT1, an epigenetic regulator, which was essential for enhanced polyfunctionality and IL-2 production.
• PRMT1 mediated increased H4R3me2a at the IL-2 promoter, boosting T cell function in vitro and in vivo.
• Wnt activation enhanced CMV-specific T cell polyfunctionality in lung transplant patient samples.

Conclusions:

• Wnt signaling epigenetically regulates T cell polyfunctionality through PRMT1.
• PRMT1 is a key mediator of enhanced T cell responses and a potential therapeutic target for immunotherapy.