Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses

Xiao, Hongkui ; Ulmert, Isabel ; Bach, Luisa ; Huber, Johanna ; Narasimhan, Hamsa ; Kurochkin, Ilia LU ; Chang, Yinshui ; Holst, Signe ; Mörbe, Urs LU and Zhang, Lili , et al. (2024) In Nature Communications 15(1).
Abstract

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a... (More)

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

(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
in
Nature Communications
volume
15
issue
1
article number
3554
publisher
Nature Publishing Group
external identifiers
  • pmid:38688934
  • scopus:85191783503
ISSN
2041-1723
DOI
10.1038/s41467-024-46966-6
language
English
LU publication?
yes
id
1e078737-faab-4f4f-9d44-9c9f00ab5773
date added to LUP
2024-05-15 12:48:36
date last changed
2024-05-29 14:38:03
@article{1e078737-faab-4f4f-9d44-9c9f00ab5773,
  abstract     = {{<p>Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8<sup>+</sup> T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.</p>}},
  author       = {{Xiao, Hongkui and Ulmert, Isabel and Bach, Luisa and Huber, Johanna and Narasimhan, Hamsa and Kurochkin, Ilia and Chang, Yinshui and Holst, Signe and Mörbe, Urs and Zhang, Lili and Schlitzer, Andreas and Pereira, Carlos Filipe and Schraml, Barbara U. and Baumjohann, Dirk and Lahl, Katharina}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-46966-6}},
  doi          = {{10.1038/s41467-024-46966-6}},
  volume       = {{15}},
  year         = {{2024}},
}