TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells.
Matthias VanderkerkenBastiaan MaesLana VandersarrenWendy ToussaintKim DeswarteManon VanheerswynghelsPhilippe PouliotLiesbet MartensSofie Van GassenConnie M ArthurMargaret E KirklingBoris ReizisDaniel ConradSean StowellHamida HammadBart N LambrechtPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.
Keyphrases
- dendritic cells
- cell proliferation
- cell cycle
- red blood cell
- immune response
- protein kinase
- regulatory t cells
- tyrosine kinase
- high fat diet induced
- induced apoptosis
- wild type
- nk cells
- bone marrow
- type diabetes
- cell cycle arrest
- stem cells
- signaling pathway
- metabolic syndrome
- endoplasmic reticulum stress
- acute kidney injury
- skeletal muscle
- hematopoietic stem cell
- sickle cell disease