Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage

Lança, Telma ; Ungerbäck, Jonas LU ; Da Silva, Clément LU ; Joeris, Thorsten LU ; Ahmadi, Fatemeh LU ; Vandamme, Julien ; Svensson-Frej, Marcus LU ; Mowat, Allan McI LU ; Kotarsky, Knut LU and Sigvardsson, Mikael LU , et al. (2022) In Immunity 55(8). p.11-1447
Abstract

Conventional dendritic cells (cDCs) consist of two major functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in committed cDC1 remains unclear. Here, we used Xcr1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identity of cDC1. In the absence of Irf8, committed cDC1 acquired the transcriptional, functional, and chromatin accessibility properties of cDC2. This conversion was independent of Irf4 and was associated with the decreased accessibility of putative IRF8, Batf3, and composite AP-1-IRF... (More)

Conventional dendritic cells (cDCs) consist of two major functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in committed cDC1 remains unclear. Here, we used Xcr1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identity of cDC1. In the absence of Irf8, committed cDC1 acquired the transcriptional, functional, and chromatin accessibility properties of cDC2. This conversion was independent of Irf4 and was associated with the decreased accessibility of putative IRF8, Batf3, and composite AP-1-IRF (AICE)-binding elements, together with increased accessibility of cDC2-associated transcription-factor-binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2-like cells.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATAC-sequencing, cDC1, cDC2, dendritic cell identity, IRF, IRF4, IRF8, transcription factor, transcriptional regulation, transcriptional reprogramming
in
Immunity
volume
55
issue
8
pages
11 - 1447
publisher
Cell Press
external identifiers
  • scopus:85135793964
  • pmid:35830859
ISSN
1074-7613
DOI
10.1016/j.immuni.2022.06.006
language
English
LU publication?
yes
id
13aaa0c1-bc03-4e73-b551-0f37dd3164fb
date added to LUP
2022-08-06 15:07:25
date last changed
2025-04-20 02:47:47
@article{13aaa0c1-bc03-4e73-b551-0f37dd3164fb,
  abstract     = {{<p>Conventional dendritic cells (cDCs) consist of two major functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in committed cDC1 remains unclear. Here, we used Xcr1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identity of cDC1. In the absence of Irf8, committed cDC1 acquired the transcriptional, functional, and chromatin accessibility properties of cDC2. This conversion was independent of Irf4 and was associated with the decreased accessibility of putative IRF8, Batf3, and composite AP-1-IRF (AICE)-binding elements, together with increased accessibility of cDC2-associated transcription-factor-binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2-like cells.</p>}},
  author       = {{Lança, Telma and Ungerbäck, Jonas and Da Silva, Clément and Joeris, Thorsten and Ahmadi, Fatemeh and Vandamme, Julien and Svensson-Frej, Marcus and Mowat, Allan McI and Kotarsky, Knut and Sigvardsson, Mikael and Agace, William W}},
  issn         = {{1074-7613}},
  keywords     = {{ATAC-sequencing; cDC1; cDC2; dendritic cell identity; IRF; IRF4; IRF8; transcription factor; transcriptional regulation; transcriptional reprogramming}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{11--1447}},
  publisher    = {{Cell Press}},
  series       = {{Immunity}},
  title        = {{IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage}},
  url          = {{http://dx.doi.org/10.1016/j.immuni.2022.06.006}},
  doi          = {{10.1016/j.immuni.2022.06.006}},
  volume       = {{55}},
  year         = {{2022}},
}