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

Abstract

AbstractThe 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-α (IFN-α–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-α–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-α 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 lymphocytes were inhibited by a neutralizing antibody to the scavenger receptor LOX-1 protein. These results unravel a novel LOX-1–dependent pathway by which IFN-α can, under both physiologic and pathologic conditions, render DCs fully competent for presenting AC-associated antigens for cross-priming CD8+ effector T cells, concomitantly with CD4+ T helper cell activation.