Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells
Emma M Carrington, Jian-Guo Zhang, Robyn M Sutherland, Ingela B Vikstrom, Jamie L Brady, Priscilla Soo, David Vremec, Cody Allison, Erinna F Lee, W Douglas Fairlie, Philippe Bouillet, Stephanie Grabow, Eleonora Ottina, Marco J Herold, Marc Pellegrini, David CS Huang, David M Tarlinton, Andreas Strasser, Andrew M Lew, Yifan Zhan
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2015
Dendritic cells (DCs) are heterogeneous, comprising subsets with functional specializations that play distinct roles in immunity as well as immunopathology. We investigated the molecular control of cell survival of two main DC subsets: plasmacytoid DCs (pDCs) and conventional DCs (cDCs) and their dependence on individual antiapoptotic BCL-2 family members. Compared with cDCs, pDCs had higher expression of BCL-2, lower A1, and similar levels of MCL-1 and BCL-XL. Transgenic overexpression of BCL-2 increased the pDC pool size in vivo with only minor impact on cDCs. With a view to immune intervention, we tested BCL-2 inhibitors and found that ABT-199 (the BCL-2 specific inhibitor) selectively ki..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) Australia
Awarded by Leukemia and Lymphoma Society Special Center of Research Grant
Awarded by NHMRC Independent Research Institutes Infrastructure Support Scheme
We thank C. Yates, M. Dayton, and M. Hancock for technical assistance. This work was supported by National Health and Medical Research Council (NHMRC) Australia Program Grants 1037321 (to A.M.L.), 1016701 (to A.S.), and 1016647 (to J.-G.Z.); Project Grants 637324 and 1007703 (to Y.Z.), 1043414 (to A.M.L.), and 104610 (to A.S.); Fellowships 1020363 (to A.S.), 1024620 (to E.F.L.), and 1080321 (to A.M.L.); the Juvenile Diabetes Research Foundation; the Rebecca L. Cooper Foundation; the Leukemia and Lymphoma Society Special Center of Research Grant 700113 (to A.S.); NHMRC Independent Research Institutes Infrastructure Support Scheme Grant 361646; Victorian State Government Operational Infrastructure Support; and the Australian government.