| First Author | Myers DR | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 8 | Pages | 1558-1571 |
| PubMed ID | 28538176 | Mgi Jnum | J:256192 |
| Mgi Id | MGI:6103296 | Doi | 10.1016/j.celrep.2017.04.076 |
| Citation | Myers DR, et al. (2017) Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells. Cell Rep 19(8):1558-1571 |
| abstractText | CD4(+) T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4(+) T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (TH2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4(+) T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4(+) T cell proliferation and uncover a suppressive role for Irf4 in TH2 polarization; halving Irf4 gene-dosage leads to increases in GATA3(+) and IL-4(+) cells. Our studies reveal that naive CD4(+) T cells are dynamically tuned by tonic LAT-HDAC7 signals. |
