IL-1β limits the extent of human 6-sulfo LacNAc dendritic cell (slanDC)-mediated NK cell activation and regulates CD95-induced apoptosis.

Abstract

To function optimally, human blood natural killer (NK) cells need to communicate with other immune cells. Previously, it has been shown that NK cells communicate with 6-sulfo LacNAc dendritic cells (slanDCs), which are able to stimulate NK cells in vitro. In this study, we investigated how slanDCs regulate the level of NK cell activation. The secretion of interleukin (IL)-1β by slanDCs during coculture with NK cells increased as a result of signaling via intercellular adhesion molecule-1 on slanDCs following its interaction with lymphocyte function-associated antigen-1 on NK cells. IL-1β induced the expression of Fas receptor (CD95) on NK cells. The binding of Fas ligand (CD178) to CD95 induced the apoptosis of activated NK cells. Moreover, IL-1β also induced increased cyclooxygenase-2 expression in slanDCs, which in turn enabled the cells to secrete prostaglandin (PG)-E2. Consequently, PGE2 acted as a suppressing agent, tuning down the activation level of NK cells. In summary, IL-1β limits the level of NK cell activation by inducing apoptosis and suppression as a homeostatic regulatory function.