A molecular network regulating the proinflammatory phenotype of human memory T lymphocytes.
Stefan EmmingNiccolò BianchiSara PollettiChiara BalestrieriCristina LeoniSara MontagnerMichele ChirichellaNicolas DelaleuGioacchino NatoliSilvia MonticelliPublished in: Nature immunology (2020)
Understanding the mechanisms that modulate helper T lymphocyte functions is crucial to decipher normal and pathogenic immune responses in humans. To identify molecular determinants influencing the pathogenicity of T cells, we separated ex vivo-isolated primary human memory T lymphocytes on the basis of their ability to produce high levels of inflammatory cytokines. We found that the inflammatory, cytokine-producing phenotype of memory T lymphocytes was defined by a specific core gene signature and was mechanistically regulated by the constitutive activation of the NF-κB pathway and by the expression of the transcriptional repressor BHLHE40. BHLHE40 attenuated the expression of anti-inflammatory factors, including miR-146a, a negative regulator of NF-κB activation and ZC3H12D, an RNase of the Regnase-1 family able to degrade inflammatory transcripts. Our data reveal a molecular network regulating the proinflammatory phenotype of human memory T lymphocytes, with the potential to contribute to disease.
Keyphrases
- endothelial cells
- working memory
- poor prognosis
- oxidative stress
- immune response
- signaling pathway
- induced pluripotent stem cells
- gene expression
- anti inflammatory
- transcription factor
- long non coding rna
- genome wide
- pluripotent stem cells
- lps induced
- dendritic cells
- regulatory t cells
- machine learning
- single molecule
- pi k akt
- staphylococcus aureus
- escherichia coli
- cystic fibrosis
- toll like receptor
- binding protein
- climate change
- long noncoding rna
- pseudomonas aeruginosa