Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses
(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)
- author
- organization
-
- LUCC: Lund University Cancer Centre
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Division of Molecular Medicine and Gene Therapy
- Cell Reprogramming in Hematopoiesis and Immunity (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- Virus Recognition (research group)
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 15
- issue
- 1
- article number
- 3554
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85191783503
- pmid:38688934
- 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
- 2024-09-19 00:46:00
@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}}, }