A molecular network regulating the proinflammatory phenotype of human memory T lymphocytes

Stefan Emming, Niccolò Bianchi, Sara Polletti, Chiara Balestrieri, Cristina Leoni, Sara Montagner, Michele Chirichella, Nicolas Delaleu, Gioacchino Natoli, Silvia Monticelli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)388-399
Number of pages12
JournalNature Immunology
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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