Conventional dendritic cells (cDCs) fulfil important local tissue functions by ensuring homeostasis and initiating de novo adaptive immune responses. As such, cDCs guide the intricate balance between immune regulation and immune induction. The development of cDCs is governed by a wide array of well-studied transcription factors (TFs). However, the transcriptional networks underlying their survival and migration are not well characterised.
The TF Bcl6 plays a role in highly proliferating cells such as germinal centre B cells, where it regulates cellular programs that ensure survival upon proliferation-associated stress. We have previously shown that deficiency of Bcl6 in cDCs leads to a significant reduction of both peripheral cDC1s and cDC2s. Moreover, the lack of Bcl6 almost completely abrogates ESAM+ cDC2s from the bridging channels of the spleen, where they, under normal circumstances, play a role in initiating germinal centre responses. Interestingly, lymph node resident cDC populations are largely unaffected, while migratory peripheral tissue-derived populations are significantly decreased by the absence of Bcl6.
We now show that the lack of Bcl6 causes cDCs to more rapidly undergo programmed cell death and that immune induction through Poly(I:C) and R848 rescues migratory cDC abundance and viability to WT levels. Functionally, a relative deficiency in migratory cDC1 correlates with a lower overall Treg frequency in the mLNs. We therefore hypothesise that Bcl6 is part of a transcriptional network supporting the maturation and migration of cDCs in the steady state. By using EdU assays and scRNA-seq, we aim to further understand the role of Bcl6 in the survival of cDCs in the later stages of their lifespan, as well as how Bcl6-deficiency affects their development and function.