Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.
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...
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doaj-fe3b793da454463fbf2dc57f27a6f47b2020-11-25T00:47:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7749010.1371/journal.pone.0077490Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.Joseph DickenAlexander MildnerDena LeshkowitzIvo P TouwShay HantisteanuSteffen JungYoram GronerClassical 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 Esam(hi) 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(+)Esam(hi) DC. Mechanistically, loss of Runx3 alters Esam(hi) DC gene expression to a signature characteristic of WT Esam(low) DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3(-/-) Esam(hi) DC capacity to prime CD4(+) T cells, attesting to the significant role of Runx3 in specifying Esam(hi) DC identity and function.http://europepmc.org/articles/PMC3817345?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joseph Dicken Alexander Mildner Dena Leshkowitz Ivo P Touw Shay Hantisteanu Steffen Jung Yoram Groner |
spellingShingle |
Joseph Dicken Alexander Mildner Dena Leshkowitz Ivo P Touw Shay Hantisteanu Steffen Jung Yoram Groner Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. PLoS ONE |
author_facet |
Joseph Dicken Alexander Mildner Dena Leshkowitz Ivo P Touw Shay Hantisteanu Steffen Jung Yoram Groner |
author_sort |
Joseph Dicken |
title |
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. |
title_short |
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. |
title_full |
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. |
title_fullStr |
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. |
title_full_unstemmed |
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. |
title_sort |
transcriptional reprogramming of cd11b+esam(hi) dendritic cell identity and function by loss of runx3. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
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 Esam(hi) 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(+)Esam(hi) DC. Mechanistically, loss of Runx3 alters Esam(hi) DC gene expression to a signature characteristic of WT Esam(low) DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3(-/-) Esam(hi) DC capacity to prime CD4(+) T cells, attesting to the significant role of Runx3 in specifying Esam(hi) DC identity and function. |
url |
http://europepmc.org/articles/PMC3817345?pdf=render |
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