Tim4 is identified as a phosphatidylserine receptor involved in the engulfment of apoptotic cells by phagocytes. In programmed cell death, apoptotic cells are engulfed by macrophages to prevent the release of harmful materials. Phosphatidylserine, exposed on the surface of apoptotic cells and nuclei from erythroid precursor cells, acts as an 'eat me' signal for phagocytes. Tim4, a type I transmembrane protein, was identified as the antigen recognized by a monoclonal antibody that inhibited phosphatidylserine-dependent engulfment of apoptotic cells. Tim4 is expressed in various mouse tissues, including spleen, lymph nodes, and fetal liver, and binds apoptotic cells via its immunoglobulin domain. Tim4 enhances the engulfment ability of fibroblasts and is involved in the engulfment of apoptotic cells by thymic macrophages. Anti-Tim4 monoclonal antibody treatment leads to the development of autoantibodies in mice. Among the Tim family members, only Tim1 and Tim4 specifically bind phosphatidylserine. Tim1 and Tim4-expressing cells bind exosomes via phosphatidylserine, and exosomes stimulate the interaction between Tim1 and Tim4. These results indicate that Tim4 and Tim1 are phosphatidylserine receptors for the engulfment of apoptotic cells and may also be involved in intercellular signaling via exosomes. MFG-E8, a protein that stimulates the engulfment of apoptotic cells, is expressed in various tissues, including peritoneal macrophages, lymph nodes, and mammary epithelial cells. A monoclonal antibody (Kat5-18) was identified that inhibits the engulfment of apoptotic cells by peritoneal macrophages. Tim4 was identified as the antigen recognized by Kat5-18 through retrovirus-mediated expression cloning. Tim4 is expressed in resident peritoneal macrophages but not in thioglycollate-elicited peritoneal macrophages. Tim4 is also expressed in spleen, thymus, lymph nodes, and salivary glands. Tim4 is expressed in Mac1+ cells, including those in the spleen, lymph nodes, and fetal liver. Tim4 enhances the engulfment of apoptotic cells by fibroblasts and is involved in the engulfment of apoptotic cells by thymic macrophages. Anti-Tim4 monoclonal antibody treatment leads to the development of autoantibodies in mice. Tim4 is a phosphatidylserine receptor that recognizes phosphatidylserine on apoptotic cells and is involved in the engulfment of apoptotic cells. Tim1 also enhances the engulfment of apoptotic cells. Tim1 is expressed in kidney tubule cells post-ischaemia, suggesting a role in removingTim4 is identified as a phosphatidylserine receptor involved in the engulfment of apoptotic cells by phagocytes. In programmed cell death, apoptotic cells are engulfed by macrophages to prevent the release of harmful materials. Phosphatidylserine, exposed on the surface of apoptotic cells and nuclei from erythroid precursor cells, acts as an 'eat me' signal for phagocytes. Tim4, a type I transmembrane protein, was identified as the antigen recognized by a monoclonal antibody that inhibited phosphatidylserine-dependent engulfment of apoptotic cells. Tim4 is expressed in various mouse tissues, including spleen, lymph nodes, and fetal liver, and binds apoptotic cells via its immunoglobulin domain. Tim4 enhances the engulfment ability of fibroblasts and is involved in the engulfment of apoptotic cells by thymic macrophages. Anti-Tim4 monoclonal antibody treatment leads to the development of autoantibodies in mice. Among the Tim family members, only Tim1 and Tim4 specifically bind phosphatidylserine. Tim1 and Tim4-expressing cells bind exosomes via phosphatidylserine, and exosomes stimulate the interaction between Tim1 and Tim4. These results indicate that Tim4 and Tim1 are phosphatidylserine receptors for the engulfment of apoptotic cells and may also be involved in intercellular signaling via exosomes. MFG-E8, a protein that stimulates the engulfment of apoptotic cells, is expressed in various tissues, including peritoneal macrophages, lymph nodes, and mammary epithelial cells. A monoclonal antibody (Kat5-18) was identified that inhibits the engulfment of apoptotic cells by peritoneal macrophages. Tim4 was identified as the antigen recognized by Kat5-18 through retrovirus-mediated expression cloning. Tim4 is expressed in resident peritoneal macrophages but not in thioglycollate-elicited peritoneal macrophages. Tim4 is also expressed in spleen, thymus, lymph nodes, and salivary glands. Tim4 is expressed in Mac1+ cells, including those in the spleen, lymph nodes, and fetal liver. Tim4 enhances the engulfment of apoptotic cells by fibroblasts and is involved in the engulfment of apoptotic cells by thymic macrophages. Anti-Tim4 monoclonal antibody treatment leads to the development of autoantibodies in mice. Tim4 is a phosphatidylserine receptor that recognizes phosphatidylserine on apoptotic cells and is involved in the engulfment of apoptotic cells. Tim1 also enhances the engulfment of apoptotic cells. Tim1 is expressed in kidney tubule cells post-ischaemia, suggesting a role in removing