Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells

• DOI: 10.1073/pnas.1417620112
• Publication Date: 2015-03-17T02:56:33Z
• Authors: 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 C. S. Huang; David M. Tarlinton; Andreas Strasser; Andrew M. Lew; Yifan Zhan
• Keywords: Bcl-2 Family

Dendritic cells (DCs) are heterogeneous, comprising subsets with functional specializations that play distinct roles in immunity as well immunopathology. We investigated the molecular control of cell survival two main DC subsets: plasmacytoid DCs (pDCs) and conventional (cDCs) their dependence on individual antiapoptotic BCL-2 family members. Compared cDCs, pDCs had higher expression BCL-2, lower A1, similar levels MCL-1 BCL-XL. Transgenic overexpression increased pDC pool size vivo only minor impact cDCs. With a view to immune intervention, we tested inhibitors found ABT-199 (the specific inhibitor) selectively killed but not Conversely, genetic knockdown A1 profoundly reduced proportion cDCs pDCs. also conditional ablation significantly both populations mice impeded DC-mediated responses. Thus, revealed types have different requirements. The basis thus advocates antagonism selective members for treating diseases pertaining subsets.