PLX227793

GSE144108: IL-12 signaling contributes to the reprogramming of neonatal CD8+ T cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8+ T lymphocytes are responsible for the elimination of infected cells. Understanding the response of these cells to normal and high stimulatory conditions is important to propose better treatments for neonates. We have previously shown that human neonatal CD8+ T cells overexpress innate inflammatory genes and have a low expression of cytotoxic and cell signaling genes. To investigate the activation potential of these cells, we evaluated the transcriptome of human neonatal and adult nave CD8+ T cells after TCR/CD28 signals +/- IL-12. We found that in neonatal cells, IL-12 signals contribute to the adult-like expression of genes associated with cell-signaling, T-cell cytokines, metabolism and cell division. Additionally, IL-12 signals contributed to the downregulation of the neutrophil signature transcription factor CEBPE and other immaturity related genes. To validate the transcriptome results, we evaluated the expression of a series of genes by RT-qPCR and the promoter methylation status on independent samples. We found that, in agreement with the transcriptome, IL-12 signals induced both the chromatin closure of neutrophil-like genes and the opening of cytotoxicity genes, suggesting that IL-12 signals contribute to the epigenetic reprogramming of neonatal lymphocytes. Furthermore, a high expression of some inflammatory genes was observed in naive and stimulated neonatal cells, in agreement with the high inflammatory profile of neonates to infections. Altogether our results point to an important contribution of IL-12 signals to the reprogramming of the neonatal CD8+ T cells. SOURCE: Darely,Yarazeth,Gutiérrez Reyna (gutierrez.darely90@gmail.com) - Laboratorio de Inmunología Celular Universidad Autónoma del Estado de Morelos