The poly(C)-binding protein Pcbp2 is essential for CD4+ T cell activation and proliferation
Massimo Martinelli,
Gabrielle Aguilar,
David S.M. Lee,
Andrew Kromer,
Nhu Nguyen,
Benjamin J. Wilkins,
Tatiana Akimova,
Ulf H. Beier,
Louis R. Ghanem
Affiliations
Massimo Martinelli
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
Gabrielle Aguilar
Division of Gastroenterology, Hepatology and Nutrition Division, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
David S.M. Lee
Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Biomedical Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
Andrew Kromer
Division of Gastroenterology, Hepatology and Nutrition Division, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Nhu Nguyen
Division of Gastroenterology, Hepatology and Nutrition Division, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Benjamin J. Wilkins
Division of Anatomic Pathology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
Tatiana Akimova
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
Ulf H. Beier
Division of Nephrology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Louis R. Ghanem
Division of Gastroenterology, Hepatology and Nutrition Division, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Summary: 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 in vivo or function in vitro. 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 in vivo Tconv cell activation in a T cell adoptive transfer colitis model system.
