Distinct translational control in CD4+ T cell subsets

• Published in: PLoS genetics 2013-05, Vol.9 (5), p.e1003494-e1003494
• Main Authors: Bjur, Eva, Larsson, Ola, Yurchenko, Ekaterina, Zheng, Lei, Gandin, Valentina, Topisirovic, Ivan, Li, Shui, Wagner, Carston R, Sonenberg, Nahum, Piccirillo, Ciriaco A
• Format: Article
• Language: English
• Subjects: Biology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell cycle; Eukaryotic Initiation Factor-4E - genetics; Flow cytometry; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; Gene expression; Gene Expression Regulation - immunology; Genomes; Humans; Immune Tolerance - genetics; Immunologi inom det medicinska området; Lymphocytes; Medical research; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Proteins; Regulation; RNA, Messenger - genetics; RNA, Messenger - immunology; Rodents; Studies; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003494

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 (T(Foxp3+)) 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 T(Foxp3)- and T(Foxp3+) 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.