Transcriptomics

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Convergence of TCR and IL-7 pathways leads to FOXO3a phosphorylation and drives the survival of C. Memory CD4+ T cells


ABSTRACT: The molecular events that are involved in the establishment and the maintenance of CD4+ Central Memory (TCM) and Effector Memory (TEM) T cells are poorly understood. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of TCM CD4+ T cells involves the activation and phosphorylation of STAT5a and FOXO3a. STAT5a phosphorylation induces the transcriptional up-regulation of anti-apoptotic genes specifically in TCM. The phosphorylation of FOXO3a at S315, following TCR engagement, prevents the transcription of pro-apoptotic gene like FasL and BIM. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of FOXO3a in protecting TCM from apoptosis. Our results define the underlying molecular mechanisms responsible for the longevity and persistence of CD4+ TCM. Keywords: comparative gene profile, cell-type comparison, central memory to Effector memory

ORGANISM(S): Homo sapiens

PROVIDER: GSE4741 | GEO | 2007/01/09

SECONDARY ACCESSION(S): PRJNA95683

REPOSITORIES: GEO

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