Martinelli Massimo, Aguilar Gabrielle, Lee David S M, Kromer Andrew, Nguyen Nhu, Wilkins Benjamin J, Akimova Tatiana, Beier Ulf H, Ghanem Louis R
Division of Gastroenterology, Hepatology and Nutrition Division, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples 80131, Italy.
iScience. 2022 Dec 21;26(1):105860. doi: 10.1016/j.isci.2022.105860. eCollection 2023 Jan 20.
The RNA-binding protein Pcbp2 is widely expressed in the innate and adaptive immune systems and is essential for mouse development. To determine whether Pcbp2 is required for CD4 T cell development and function, we derived mice with conditional Pcbp2 deletion in CD4 T cells and assessed their overall phenotype and proliferative responses to activating stimuli. We found that Pcbp2 is essential for T conventional cell (Tconv) proliferation, working through regulation of co-stimulatory signaling. Pcbp2 deficiency in the CD4 lineage did not impact Treg abundance or function . In addition, our data demonstrate a clear association between Pcbp2 control of Runx1 exon 6 splicing in CD4 T cells and a specific role for Pcbp2 in the maintenance of peripheral CD4 lymphocyte population size. Last, we show that Pcbp2 function is required for optimal Tconv cell activation in a T cell adoptive transfer colitis model system.
RNA 结合蛋白 Pcbp2 在固有免疫系统和适应性免疫系统中广泛表达，对小鼠发育至关重要。为了确定 CD4 T 细胞的发育和功能是否需要 Pcbp2，我们培育了在 CD4 T 细胞中条件性缺失 Pcbp2 的小鼠，并评估了它们的整体表型以及对激活刺激的增殖反应。我们发现，Pcbp2 通过调节共刺激信号传导，对传统 T 细胞（Tconv）增殖至关重要。CD4 谱系中 Pcbp2 的缺失并不影响调节性 T 细胞（Treg）的丰度或功能。此外，我们的数据表明，CD4 T 细胞中 Pcbp2 对 Runx1 外显子 6 剪接的控制与 Pcbp2 在维持外周 CD4 淋巴细胞群体大小方面的特定作用之间存在明确关联。最后，我们表明，在 T 细胞过继转移结肠炎模型系统中，最佳 Tconv 细胞激活需要 Pcbp2 发挥功能。
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