期刊
IMMUNITY
卷 27, 期 6, 页码 927-940出版社
CELL PRESS
DOI: 10.1016/j.immuni.2007.11.011
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资金
- NIAID NIH HHS [P01 AI054456, P01 AI054456-010002, P01 AI054456-019001] Funding Source: Medline
- NINDS NIH HHS [R01 NS045937-02, R01 NS045937-01, R01 NS045937-04, R01 NS045937, R01 NS045937-05, R01 NS045937-03] Funding Source: Medline
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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