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

被引:1
作者
Martinelli, Massimo [1 ,2 ]
Aguilar, Gabrielle [1 ]
Lee, David S. M. [4 ,5 ]
Kromer, Andrew [1 ]
Nguyen, Nhu [1 ]
Wilkins, Benjamin J. [6 ,7 ]
Akimova, Tatiana [7 ]
Beier, Ulf H. [8 ,9 ]
Ghanem, Louis R. [1 ,3 ,9 ]
机构
[1] Childrens Hosp Philadelphia, Div Gastroenterol, Hepatol & Nutr Div, Philadelphia, PA 19104 USA
[2] Univ Naples Federico II, Dept Translat Med Sci, Sect Pediat, I-80131 Naples, Italy
[3] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA
[4] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA
[5] Univ Penn, Perelman Sch Med, Inst Biomed Informat, Philadelphia, PA 19104 USA
[6] Childrens Hosp Philadelphia, Div Anat Pathol, Philadelphia, PA 19104 USA
[7] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[8] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA
[9] Janssen Res & Dev, 1400 McKean Rd, Spring House, PA 19477 USA
关键词
NF-KAPPA-B; MESSENGER-RNA; GENE-EXPRESSION; BINDING; DIFFERENTIATION; REPRESSION; COMPLEX; RUNX1; IDENTIFICATION; STABILIZATION;
D O I
10.1016/j.isci.2022.105860
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:23
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