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Immunity 2007 Dec;27(6):927-40

TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells.

Kobayashi N, Karisola P, Peña-Cruz V, Dorfman DM, Jinushi M, Umetsu SE, Butte MJ, Nagumo H, Chernova I, Zhu B, Sharpe AH, Ito S, Dranoff G, Kaplan GG, Casasnovas JM, Umetsu DT, Dekruyff RH, Freeman GJ

Freeman GJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain


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.

Category: Journal Article
PubMed ID: #18082433
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29