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

共 40 条

[1] Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice [J].

Asano, K ;

Miwa, M ;

Miwa, K ;

Hanayama, R ;

Nagase, H ;

Nagata, S ;

Tanaka, M .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (04) :459-467

[2] Immune clearance of phosphatidylserine-expressing cells by phagocytes -: The role of β2-glycoprotein I in macrophage recognition [J].

Balasubramanian, K ;

Chandra, J ;

Schroit, AJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (49) :31113-31117

[3] High-throughput phagocytosis assay utilizing a pH-sensitive fluorescent dye [J].

Beletskii, A ;

Cooper, M ;

Sriraman, P ;

Chiriac, C ;

Zhao, LH ;

Abbot, S ;

Yu, LM .

BIOTECHNIQUES, 2005, 39 (06) :894-897

[4] Human TIM-1 associates with the TCR complex and up-regulates T cell activation signals [J].

Binne, Lauri L. ;

Scott, Martin L. ;

Rennert, Paul D. .

JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4342-4350

[5] Macrophage recognition of externalized phosphatidylserine and phagocytosis of apoptotic Jurkat cells - existence of a threshold [J].

Borisenko, GG ;

Matsura, T ;

Liu, SX ;

Tyurin, VA ;

Jiang, JF ;

Serinkan, FB ;

Kagan, VE .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2003, 413 (01) :41-52

[6] T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface [J].

Cao, Erhu ;

Zang, Xingxing ;

Ramagopal, Udupi A. ;

Mukhopadhaya, Arunika ;

Fedorov, Alexander ;

Fedorov, Elena ;

Zencheck, Wendy D. ;

Lary, Jeffrey W. ;

Cole, James L. ;

Deng, Haiteng ;

Xiao, Hui ;

DiLorenzo, Teresa P. ;

Allison, James P. ;

Nathenson, Stanley G. ;

Almo, Haiteng C. .

IMMUNITY, 2007, 26 (03) :311-321

[7] Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase [J].

Cohen, PL ;

Caricchio, R ;

Abraham, V ;

Camenisch, TD ;

Jennette, JC ;

Roubey, RAS ;

Earp, HS ;

Matsushima, G ;

Reap, EA .

JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (01) :135-140

[8] Epitope-dependent effect of anti-murine TIM-1 monoclonal antibodies on T cell activity and lung immune responses [J].

D Sizing, Irene ;

Bailly, Veronique ;

McCoon, Patricia ;

Chang, Wenjie ;

Rao, Sambasiva ;

Pablo, Lourdes ;

Rennard, Rachel ;

Walsh, Meghan ;

Li, Zhifang ;

Zafari, Mohammad ;

Dobles, Max ;

Tarilonte, Leticia ;

Miklasz, Steven ;

Majeau, Gerard ;

Godbout, Kevin ;

Scott, Martin L. ;

Rennert, Paul D. .

JOURNAL OF IMMUNOLOGY, 2007, 178 (04) :2249-2261

[9] T cell Ig and mucin 1 (TIM-1) is expressed on in vivo-activated T cells and provides a costimulatory signal for T cell activation [J].

de Souza, AJ ;

Oriss, TB ;

O'Malley, KJ ;

Ray, A ;

Kane, LP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (47) :17113-17118

[10] Loss of expression of the WNT/β-catenin-signaling pathway transcription factors lymphoid enhancer factor-1 (LEF-1) and T cell factor-1 (TCF-1) in a subset of peripheral T cell lymphomas [J].

Dorfman, DM ;

Greisman, HA ;

Shahsafaei, A .

AMERICAN JOURNAL OF PATHOLOGY, 2003, 162 (05) :1539-1544

← 1 2 3 4 →