Apoptosis and NET formation in the pathogenesis of SLE.
Systemic Lupus Erythematosus is an autoimmune disease characterized by the formation of anti-nuclear autoantibodies, particularly anti-chromatin. Although the aetiology of the disease has not yet been fully elucidated, several mechanisms have been proposed to be involved. Due to an aberrant apoptosis or decreased removal of apoptotic cells, apoptotic blebs containing chromatin are released. During apoptosis, chromatin is modified that increases its immunogenicity. Myeloid dendritic cells (myDC) can take up apoptotic blebs and stimulate autoreactive T helper cells, and subsequently the formation of autoantibodies by autoreactive B cells. Immune complexes formed by anti-chromatin autoantibodies and modified chromatin deposit on basal membranes, and incite a local inflammation, but can also stimulate plasmacytoid dendritic cells to produce IFN-α. In addition to apoptotic blebs, neutrophil extracellular traps released by dying neutrophils, in a process called NETosis, may serve as a source of autoantigens as well. In this review, we describe the role of both apoptosis and NETosis in the pathogenesis of SLE, and show how both processes may interact with each other.
Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Yvette M
YM
Bouts
David F G J
DF
Wolthuis
Michiel F M
MF
Dirkx
Elmar
E
Pieterse
Esther M F
EM
Simons
Anna M
AM
van Boekel
Jürgen W
JW
Dieker
Johan
J
van der Vlag
D000974:Antibodies, Antinuclear / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology; D002843:Chromatin / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D002843:Chromatin; D016898:Interferon-alpha