@article {542416, title = {TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells.}, journal = {Immunity}, volume = {27}, number = {6}, year = {2007}, month = {2007 Dec}, pages = {927-40}, abstract = {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.}, keywords = {Animals, Apoptosis, Dendritic Cells, Humans, Lymphocyte Activation, Macrophages, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, NIH 3T3 Cells, Phagocytosis, Phosphatidylserines, Receptors, Virus, T-Lymphocytes}, issn = {1074-7613}, doi = {10.1016/j.immuni.2007.11.011}, author = {Kobayashi, Norimoto and Karisola, Piia and Pe{\~n}a-Cruz, Victor and Dorfman, David M and Jinushi, Masahisa and Umetsu, Sarah E and Butte, Manish J and Nagumo, Haruo and Chernova, Irene and Zhu, Baogong and Sharpe, Arlene H and Ito, Susumu and Dranoff, Glenn and Kaplan, Gerardo G and Casasnovas, Jose M and Umetsu, Dale T and DeKruyff, Rosemarie H and Freeman, Gordon J} }