The poly(C)-binding protein Pcbp2 is essential for CD4⁺ T cell activation and proliferation

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The RNA-binding protein Pcbp2 is broadly expressed across immune cells.
• Pcbp2 plays a vital role in mouse development.
• Its specific function in CD4+ T cell subsets requires elucidation.

Purpose of the Study:

• To investigate the necessity of Pcbp2 for CD4+ T cell development and function.
• To explore Pcbp2's role in T conventional (Tconv) and regulatory T (Treg) cell biology.
• To understand Pcbp2's impact on T cell signaling and peripheral lymphocyte homeostasis.

Main Methods:

• Generation of mice with conditional Pcbp2 deletion in CD4+ T cells.
• Assessment of T cell phenotype, proliferation, and co-stimulatory signaling.
• Analysis of Treg abundance and function.
• Investigation of Pcbp2's role in Runx1 splicing.
• Evaluation of Tconv cell activation in a colitis model.

Main Results:

• Pcbp2 is essential for Tconv cell proliferation via co-stimulatory signaling regulation.
• Pcbp2 deficiency does not affect Treg abundance or function.
• Pcbp2 controls Runx1 exon 6 splicing in CD4+ T cells.
• Pcbp2 is critical for maintaining peripheral CD4+ lymphocyte population size.
• Pcbp2 is required for optimal in vivo Tconv cell activation during colitis.

Conclusions:

• Pcbp2 is indispensable for CD4+ Tconv cell proliferation and optimal in vivo activation.
• Pcbp2 regulates T cell homeostasis through control of Runx1 splicing.
• Pcbp2 is a key regulator of adaptive immune responses, particularly in CD4+ T cells.