TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells
Proceedings of the National Academy of Sciences of the United States of America , Volume 117 - Issue 49 p. 31331- 31342
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.
|Proceedings of the National Academy of Sciences of the United States of America|
|Organisation||Department of Pulmonology|
Vanderkerken, M. (Matthias), Maes, B. (Bastiaan), Vandersarren, L. (Lana), Toussaint, W, Deswarte, K, van Heerswynghels, M, … Lambrecht, B.N.M. (2020). TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 117(49), 31331–31342. doi:10.1073/pnas.2009847117