Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8 Dendritic Cells.

Apoptotic cell death of Dendritic cells (DCs) is critical for immune homeostasis. Although intrinsic mechanisms controlling DC death have not been fully characterized up to now, experimentally enforced inhibition of DC-death causes various autoimmune diseases in model systems. We have generated mice deficient for (Ppef2), which is selectively expressed in CD8 DCs, but not in other related DC subtypes such as tissue CD103 DCs. Ppef2 is down-regulated rapidly upon maturation of DCs by toll-like receptor stimuli, but not upon triggering of CD40. Ppef2-deficient CD8 DCs accumulate the pro-apoptotic (Bim) and show increased apoptosis and reduced competitve repopulation capacities. Furthermore, CD8 DCs have strongly diminished antigen presentation capacities , as CD8 T cells primed by CD8 DCs undergo reduced expansion. In conclusion, our data suggests that Ppef2 is crucial to support survival of immature CD8 DCs, while Ppef2 down-regulation during DC-maturation limits T cell responses.

PMID: 30809231