GSE113949
Comparison of transcriptome between E8I knock-out and wild type mouse during CD4 CTL polarization in vitro
The expression of key transcription factors drives CD4 T cells to develop into functional T helper (Th) subsets, each characterized by secretion of particular cytokines.  This process is critical for normal immune function.  CD4 T cells can also reprogram to cytotoxic T lymphocytes (CTL), but the key transcriptional mechanism that controls this process has not been defined.  Cytokine TGFb, an important regulator of CD4 Th subset differentiation induces the master transcription factor, Foxp3 in induced regulatory T cells (iTreg) or Rorc in IL-17-secreting T cells (Th17 cells).  TGFb is also important for the CD4 CTL differentiation, characterized by T-BET and RUNX3 expression whereas Foxp3 and Rorc genes are repressed in these cells. Here we identify, a long intergenic noncoding RNA transcribed from the Cd8 locus (Cd8LncRNA), as critical for the coordinated expression and function of T-BET and RUNX3 combined with Foxp3 and Rorc suppression in CD4 CTL. Since this LncRNA overlaps CD8 locus enhancer (E8I), we first analyzed the effect of LncRNA deletion for CD4 T cell polarization using E8I knock-out mouse. These findings define Cd8LincRNA as a key controller of the helper versus cytotoxic gene expression profile in differentiating CD4 effector T cells. The action of this LncRNA adds another layer of regulation of CD4 T cell functions and expands the opportunity to define new drug targets for the treatment of cancers, infections and inflammatory diseases. Overall design: mRNA profiles of wild type (WT) and E8IKO (PMID:9806635) mice during CD4 CTL differentiation in vitro were generated by RNA sequencing.