Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2020-11-19 , DOI: 10.1073/pnas.2009847117 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 Conrad, Sean Stowell, Hamida Hammad, Bart N. Lambrecht
Antigen-presenting conventional dendritic cells (cDCs) are broadly divided into type 1 and type 2 subsets that further adapt their phenotype and function to perform specialized tasks in the immune system. The precise signals controlling tissue-specific adaptation and differentiation of cDCs are currently poorly understood. We found that mice deficient in the Ste20 kinase Thousand and One Kinase 3 (TAOK3) lacked terminally differentiated ESAM+ CD4+ cDC2s in the spleen and failed to prime CD4+ T cells in response to allogeneic red-blood-cell transfusion. These NOTCH2- and ADAM10-dependent cDC2s were absent selectively in the spleen, but not in the intestine of Taok3−/− and CD11c-cre Taok3fl/fl mice. The loss of splenic ESAM+ cDC2s was cell-intrinsic and could be rescued by conditional overexpression of the constitutively active NOTCH intracellular domain in CD11c-expressing cells. Therefore, TAOK3 controls the terminal differentiation of NOTCH2-dependent splenic cDC2s.