Loss of Bcl6 transcriptionally alters classical dendritic cells and diminishes T follicular helper cell-inducing cDC2 in mouse spleen

Xiao, H.; Ulmert, I.; Narasimhan, H.; Kurochkin, I.; Moerbe, U.; Baumjohann, D.; Pereira, F.; Schraml, B.; Lahl, K.

doi:10.1101/2022.08.10.503322

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bioRxiv · 10.1101/2022.08.10.503322

Loss of Bcl6 transcriptionally alters classical dendritic cells and diminishes T follicular helper cell-inducing cDC2 in mouse spleen

Xiao, H.·Ulmert, I.·Narasimhan, H.·Kurochkin, I.·Moerbe, U.·Baumjohann, D.·Pereira, F.·Schraml, B.·Lahl, K.

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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 cDC1s and cDC2s, while their lineage identity is preserved. Bcl6-deficient cDC1s 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 cDCs causes a complete loss of Notch2-dependent cDC2s 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.

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Xiao, H., Ulmert, I., Narasimhan, H., Kurochkin, I., Moerbe, U., Baumjohann, D., Pereira, F., Schraml, B., Lahl, K.. 2022-08-12. Loss of Bcl6 transcriptionally alters classical dendritic cells and diminishes T follicular helper cell-inducing cDC2 in mouse spleen. https://doi.org/10.1101/2022.08.10.503322

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