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

被引：530

作者：

Kobayashi, Norimoto ^{[1
,2
]}

Karisola, Piia ^{[3
]}

Pena-Cruz, Victor ^{[1
,2
]}

Dorfman, David M. ^{[4
]}

Jinushi, Masahisa ^{[1
,2
]}

Umetsu, Sarah E. ^{[5
]}

Butte, Manish J. ^{[6
]}

Nagumo, Haruo ^{[1
,2
]}

Chernova, Irene ^{[1
,2
]}

Zhu, Baogong ^{[1
,2
]}

Sharpe, Arlene H. ^{[6
]}

Ito, Susumu ^{[7
]}

Dranoff, Glenn ^{[1
,2
]}

Kaplan, Gerardo G. ^{[8
]}

Casasnovas, Jose M. ^{[9
]}

Umetsu, Dale T. ^{[3
]}

Dekruyff, Rosemarie H. ^{[3
]}

Freeman, Gordon J. ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[5] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA

[6] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[8] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

[9] CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain

来源：

IMMUNITY | 2007年 / 27卷 / 06期

关键词：

D O I：

10.1016/j.immuni.2007.11.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：927 / 940

页数：14

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