| First Author | Villar J | Year | 2023 |
| Journal | Nat Immunol | Volume | 24 |
| Issue | 1 | Pages | 84-95 |
| PubMed ID | 36543959 | Mgi Jnum | J:337690 |
| Mgi Id | MGI:7495962 | Doi | 10.1038/s41590-022-01374-0 |
| Citation | Villar J, et al. (2023) ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment. Nat Immunol 24(1):84-95 |
| abstractText | 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. |
