TY - JOUR
T1 - Distinct Translational Control in CD4+ T Cell Subsets
AU - Bjur, Eva
AU - Larsson, Ola
AU - Yurchenko, Ekaterina
AU - Zheng, Lei
AU - Gandin, Valentina
AU - Topisirovic, Ivan
AU - Li, Shui
AU - Wagner, Carston R.
AU - Sonenberg, Nahum
AU - Piccirillo, Ciriaco A.
PY - 2013/5
Y1 - 2013/5
N2 - Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression studies have defined canonical signatures of T cell subsets. Changes in steady-state mRNA levels, however, often do not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3- non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3- and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4+ T cell subsets.
AB - Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression studies have defined canonical signatures of T cell subsets. Changes in steady-state mRNA levels, however, often do not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3- non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3- and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4+ T cell subsets.
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U2 - 10.1371/journal.pgen.1003494
DO - 10.1371/journal.pgen.1003494
M3 - Article
C2 - 23658533
AN - SCOPUS:84878513440
SN - 1553-7390
VL - 9
JO - PLoS genetics
JF - PLoS genetics
IS - 5
M1 - e1003494
ER -