Investigating the role of ZEB transcription factors in cDC biology

01 January 2019 → 31 December 2022
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Immunology
    • Immunology
    • Immunology
Project description

Dendritic cells (cDCs) play a critical role in the immune response. They sample the environment and
instruct other immune cells to respond correctly. There are 2 main types, cDC1s and cDC2s, but the
cDC2 population can be further subdivided into different subtypes. However, the way we divide
these cells is not conserved across tissues making it unclear how one subtype relates to another.
Moreover, it is unclear if this subdivision of cDC2s is functionally relevant for the immune response.
Different types of cDCs are regulated by transcription factors (TFs), which control the way the
genetic information in each cell is read. We have recently found a role for the TF ZEB2 in cDC2
biology, with ZEB2 being required for the presence of at least some cDC2s in each tissue. Here, we
aim to build on this work and further understand the role of the ZEB TFs in cDC biology. For cDC2s,
we aim to study the different subtypes in each tissue, determine which are governed by ZEB2, and
investigate their specific functions. Additionally, we have identified that ZEB1, the family member of
ZEB2, is crucial for the presence and type of cDC1s in the spleen. Loss of ZEB1 from cDC1s also
effects the type of cDC2s in the spleen. Thus, here we also aim to examine how ZEB1 achieves this.
Together, this project aims to better understand cDC biology, paving the way for better therapeutic
strategies in the clinic.