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<p>The transcriptional program that regulates immunosuppression in CCR7<sup>+</sup> 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<sup>+</sup> 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&amp;TAG analysis suggests that EHF directly regulate <i>Ccr7</i>, <i>Cd200</i>, <i>Cd274</i>, <i>Irf4</i> and <i>Rel</i> expression. Additionally, single-cell RNA-sequencing demonstrates that <i>Ehf</i> expression is highly enriched in CCR7<sup>hi</sup> DCs in mice and humans. Our study thus reveals a conserved transcriptional program that regulates cDC maturation and immunosuppression.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Xiaoli Liu,
  • Ling Wang,
  • Yongfang Xiao,
  • Hai Ni,
  • Jiancheng Huang,
  • Kai Yao,
  • Wei Zhao,
  • Jian-Rong Yang,
  • Jijun Zhao,
  • Angela R. Wu,
  • Cliff Y. Yang

摘要

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.