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TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells.

ABSTRACT: 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 Taok3 ^fl/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.

SUBMITTER: Vanderkerken M

PROVIDER: S-EPMC7733863 | biostudies-literature |

REPOSITORIES: biostudies-literature

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2013-09-19 | E-GEOD-43456 | biostudies-arrayexpress

Cytokine-dependent dendritic cell differentiation in the splenic microenvironment

2013-09-19 | GSE43456 | GEO

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