Conventional dendritic cells (cDCs) exist as cDC1s and cDC2s and develop from precursors through the concerted action of distinct transcription factors (TFs). Recently, the ZEB family of TFs have been added to the list of TFs mediating cDC development as we and others, have shown that ZEB2 regulates the decision to become a cDC2. Additionally, our data also suggest that its homolog, ZEB1, is a critical cDC TF, specifically regulating splenic cDC1 biology. Unexpectedly, loss of ZEB1 from cDC1s also leads to a reduction in NK and NKT cells and an almost complete ablation of macrophages in the spleen, suggesting a complex interplay between cDC1s and these cell types in this specific microenvironment. Here, I aim to dissect the precise mechanisms and consequences of this role of ZEB1. Using transcriptomics and spatial proteogenomics approaches, I will examine how this phenotype is mediated by ZEB1 expression in cDC1s. By assessing the antigen-presenting potential of cDCs and the systemic response to infection, I will investigate the functional consequences of ZEB1-deficiency in cDC1s. Finally, to understand how and why ZEB1 expression appears to only control splenic cDC1 biology despite its widespread expression across cDC1s, I will utilize a combination of transcriptomic and epigenetics approaches. Together, this project will gain a fundamental understanding of the role of ZEB1 in cDC1 biology, and the complex cell-cell interactions mediated by cDC1s in the spleen.