# The transcription factor EHF promotes the maturation and immunosuppression of conventional dendritic cells

## TL;DR

This study identifies EHF as a key transcription factor that controls the maturation and immunosuppressive function of dendritic cells in mice and humans.

## Contribution

The paper reveals EHF as a novel regulator of dendritic cell maturation and immunosuppression through transcriptional control.

## Key findings

- EHF deletion in dendritic cells increases resistance to autoimmune, infection, and tumor challenges.
- EHF regulates the expression of CCR7, CD200, PD-L1, IRF4, and Rel in dendritic cells.
- EHF overexpression promotes immunosuppression, while its deletion leads to Th1- and Th17-biased T cell responses.

## Abstract

The transcriptional program that regulates immunosuppression in CCR7+ conventional dendritic cells (cDCs) is currently unknown. Here, we identify ETS homologous factor (EHF) as a transcription factor that regulates cDC maturation and immunosuppression after TLR7/8/9 stimulation. Mice with conditional deletion of EHF in DCs exhibit increased resistance to autoimmune, infection or tumor challenge. EHF-deficient DCs promotes Th1- and Th17-biased CD4+ helper T cell response in vivo and in vitro. EHF-deficient cDC1s and cDC2s exhibit decreased expression of CCR7, CD200 and PD-L1, increased expression of DC-lineage transcriptional factor IRF4, and decreased expression of inhibitory NFκB family member Rel. EHF overexpression in DCs results in the opposite phenotype. CUT&TAG analysis suggests that EHF directly regulate Ccr7, Cd200, Cd274, Irf4 and Rel expression. Additionally, single-cell RNA-sequencing demonstrates that Ehf expression is highly enriched in CCR7hi DCs in mice and humans. Our study thus reveals a conserved transcriptional program that regulates cDC maturation and immunosuppression.

The transcriptional program that regulates immunosuppression in conventional dendritic cells needs exploration. The authors here identify ETS homologous factor (EHF) as a transcription factor that regulates cDC maturation and functions, with its deletion limits while its overexpression promotes cDCs immunosuppression function both in vitro and in vivo.