[HTML][HTML] TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells

N Kobayashi, P Karisola, V Peņa-Cruz, DM Dorfman… - Immunity, 2007 - cell.com
N Kobayashi, P Karisola, V Peņa-Cruz, DM Dorfman, M Jinushi, SE Umetsu, MJ Butte
Immunity, 2007cell.com
The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance.
Here we showed that TIM-4 is expressed on human and mouse macrophages and dendritic
cells, and both TIM-4 and TIM-1 specifically bound phosphatidylserine (PS) on the surface of
apoptotic cells but not any other phospholipid tested. TIM-4+ peritoneal macrophages, TIM-
1+ kidney cells, and TIM-4-or TIM-1-transfected cells efficiently phagocytosed apoptotic
cells, and phagocytosis could be blocked by TIM-4 or TIM-1 monoclonal antibodies …
Summary
The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. Here we showed that TIM-4 is expressed on human and mouse macrophages and dendritic cells, and both TIM-4 and TIM-1 specifically bound phosphatidylserine (PS) on the surface of apoptotic cells but not any other phospholipid tested. TIM-4+ peritoneal macrophages, TIM-1+ kidney cells, and TIM-4- or TIM-1-transfected cells efficiently phagocytosed apoptotic cells, and phagocytosis could be blocked by TIM-4 or TIM-1 monoclonal antibodies. Mutations in the unique cavity of TIM-4 eliminated PS binding and phagocytosis. TIM-4 mAbs that blocked PS binding and phagocytosis mapped to epitopes in this binding cavity. These results show that TIM-4 and TIM-1 are immunologically restricted members of the group of receptors whose recognition of PS is critical for the efficient clearance of apoptotic cells and prevention of autoimmunity.
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