LOX-1 as a natural IFN-α-mediated signal for apoptotic cell uptake and antigen presentation in dendritic cells

The identification of molecules responsible for apoptotic cell (AC) uptake by dendritic cells (DCs) and induction of T-cell immunity against AC-associated antigens is a challenge in immunology. DCs differentiated in the presence of interferon-alpha (IFN-alpha-conditioned DCs) exhibit a marked phagocytic activity and a special attitude in inducing CD8(+) T-cell response. In this study, we found marked overexpression of the scavenger receptor oxidized low-density lipoprotein receptor 1 (LOX-1) in IFN-alpha-conditioned DCs, which was associated with increased levels of genes belonging to immune response families and high competence in inducing T-cell immunity against antigens derived from allogeneic apoptotic lymphocytes. In particular, the capture of ACs by IFN-alpha DCs led to a substantial subcellular rearrangement of major histocompatibility complex class I and class II molecules, along with enhanced cross-priming of autologous CD8(+) T cells and CD4(+) T-cell activation. Remarkably, AC uptake, CD8(+) T-cell cross-priming, and, to a lesser extent, priming of CD4(+) T phocytes were inhibited by a antibody to the scavenger receptor LOX-1 protein. These results unravel a LOX-1-dependent pathway by IFN-alpha can, under both physiologic pathologic conditions, render DCs competent for presenting AC-associated antigens for cross-priming CD8(+) T cells, concomitantly with CD4(+) helper cell activation. (Blood. 2010;1554-1563)