LOX-1 as a natural IFN-alpha-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 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-alpha 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.
Parlato
Stefania
S
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.
Romagnoli
Giulia
G
Spadaro
Francesca
F
Canini
Irene
I
Sirabella
Paolo
P
Borghi
Paola
P
Ramoni
Carlo
C
Filesi
Ilaria
I
Biocca
Silvia
S
Gabriele
Lucia
L
Belardelli
Filippo
F
D017951:Antigen Presentation / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051127:Scavenger Receptors, Class E / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
D007155:Immunologic Factors; D016898:Interferon-alpha; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E