The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes - Archive ouverte HAL
Article Dans Une Revue eLife Année : 2018

The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes

Yasmina Serroukh
  • Fonction : Auteur
Chunyan Gu-Trantien
  • Fonction : Auteur
Baharak Hooshiar Kashani
  • Fonction : Auteur
Abdulkader Azouz
  • Fonction : Auteur
Aurelie Detavernier
  • Fonction : Auteur
Alice Hoyois
  • Fonction : Auteur
Jishnu Das
  • Fonction : Auteur
Emeline Pollet
  • Fonction : Auteur
Tressy Tabbuso
  • Fonction : Auteur
Klaas Van Gisbergen
  • Fonction : Auteur
Marc Dalod
Stanislas Goriely
  • Fonction : Auteur
Arnaud Marchant
  • Fonction : Auteur

Résumé

Cytotoxic CD4 (CD4(CTX)) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4(CTX)-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4(CTX) T cells and identifies potential targets for immunotherapy against viral infections and cancer.

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Immunologie
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hal-02118048 , version 1 (18-10-2024)

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Yasmina Serroukh, Chunyan Gu-Trantien, Baharak Hooshiar Kashani, Matthieu Defrance, Thien-Phong Vu Manh, et al.. The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes. eLife, 2018, 7, pp.e30496. ⟨10.7554/eLife.30496⟩. ⟨hal-02118048⟩

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