Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells.
Phagocytosis of apoptotic cells by macrophages and dendritic cells is necessary for clearance of proinflammatory debris and for presentation of viral, tumor, and self Ags. While a number of receptors involved in the cognate recognition of apoptotic cells by phagocytes have been identified, the signaling events that result in internalization remain poorly understood. Here we demonstrate that clearance of apoptotic cells is accompanied by recruitment of the Wiskott-Aldrich syndrome (WAS) protein to the phagocytic cup and that it's absence results in delayed phagocytosis both in vitro and in vivo. Therefore, we propose that WAS protein plays an important and nonredundant role in the safe removal of apoptotic cells and that deficiency contributes significantly to the immune dysregulation of WAS. The efficiency of apoptotic cell clearance may be a key determinant in the suppression of tissue inflammation and prevention of autoimmunity.
Leverrier
Y
Y
Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, London, United Kingdom.
Lorenzi
R
R
Blundell
M P
MP
Brickell
P
P
Kinnon
C
C
Ridley
A J
AJ
Thrasher
A J
AJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D019169:Jurkat Cells; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D051316:Wiskott-Aldrich Syndrome Protein
D007074:Immunoglobulin G; D009895:Opsonin Proteins; D011506:Proteins; C495767:WAS protein, human; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein