Significance Dendritic cells (DC) play a crucial role in the immune system by bridging innate and adaptive immunity. In the spleen, a specific subset of DCs accumulates around the blood-filtering marginal zone to capture particulate antigens such as red blood cells. We show here that these specialized DCs develop in response to NOTCH2 instruction that is regulated by a poorly studied kinase, called Thousand and One Kinase 3 (TAOK3). This kinase controls DC development in a cell-intrinsic manner, rendering cells receptive to NOTCH2 signaling. Interfering with this kinase opens up ways to manipulate a specific subset of DCs.