ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Nature Immunology Year : 2023

ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment

Javiera Villar
Adeline Cros
  • Function : Author
Alba de Juan
  • Function : Author
Pierre-Emmanuel Bonte
Ioanna Tiniakou
Boris Reizis
Elodie Segura
  • Function : Author
  • PersonId : 943749

Abstract

In inflamed tissues, monocytes differentiate into macrophages (mo-Macs) or dendritic cells (mo-DCs). In chronic nonresolving inflammation, mo-DCs are major drivers of pathogenic events. Manipulating monocyte differentiation would therefore be an attractive therapeutic strategy. However, how the balance of mo-DC versus mo-Mac fate commitment is regulated is not clear. In the present study, we show that the transcriptional repressors ETV3 and ETV6 control human monocyte differentiation into mo-DCs. ETV3 and ETV6 inhibit interferon (IFN)-stimulated genes; however, their action on monocyte differentiation is independent of IFN signaling. Instead, we find that ETV3 and ETV6 directly repress mo-Mac development by controlling MAFB expression. Mice deficient for Etv6 in monocytes have spontaneous expression of IFN-stimulated genes, confirming that Etv6 regulates IFN responses in vivo. Furthermore, these mice have impaired mo-DC differentiation during inflammation and reduced pathology in an experimental autoimmune encephalomyelitis model. These findings provide information about the molecular control of monocyte fate decision and identify ETV6 as a therapeutic target to redirect monocyte differentiation in inflammatory disorders.
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Dates and versions

inserm-03994135 , version 1 (17-02-2023)

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Javiera Villar, Adeline Cros, Alba de Juan, Lamine Alaoui, Pierre-Emmanuel Bonte, et al.. ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment. Nature Immunology, 2023, 24 (1), pp.84-95. ⟨10.1038/s41590-022-01374-0⟩. ⟨inserm-03994135⟩
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