Transcriptional Reprogramming of CD11b+Esamhi Dendritic Cell Identity and Function by Loss of Runx3

Joseph Dicken, Alexander Mildner, Dena Leshkowitz, Ivo P. Touw, Shay Hantisteanu, Yoram Groner, Steffen Jung

Research output: Contribution to journalArticlepeer-review

Abstract

Classical dendritic cells (cDC) are specialized antigen-presenting cells mediating immunity and tolerance. cDC cell-lineage decisions are largely controlled by transcriptional factor regulatory cascades. Using an in vivo cell-specific targeting of Runx3 at various stages of DC lineage development we show that Runx3 is required for cell-identity, homeostasis and function of splenic Esamhi DC. Ablation of Runx3 in DC progenitors led to a substantial decrease in splenic CD4+/CD11b+ DC. Combined chromatin immunoprecipitation sequencing and gene expression analysis of purified DC-subsets revealed that Runx3 is a key gene expression regulator that facilitates specification and homeostasis of CD11b+Esamhi DC. Mechanistically, loss of Runx3 alters Esamhi DC gene expression to a signature characteristic of WT Esamlow DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3-/- Esamhi DC capacity to prime CD4+ T cells, attesting to the significant role of Runx3 in specifying Esamhi DC identity and function.

Original languageEnglish
Article numbere77490
JournalPLoS ONE
Volume8
Issue number10
DOIs
StatePublished - 15 Oct 2013

All Science Journal Classification (ASJC) codes

  • General
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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