TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells
Matthias Vanderkerken, Bastiaan Maes, Lana Vandersarren, Wendy Toussaint, Kim Deswarte, Manon Vanheerswynghels, Philippe Pouliot, Liesbet Martens, Sofie Van Gassen, Connie M. Arthur, Margaret E. Kirkling, Boris Reizis, Daniel H. Conrad, Sean R. Stowell, Hamida Hammad, Bart N. Lambrecht
Abstract
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.