TY - JOUR
T1 - Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation
AU - Nakayama, Masafumi
AU - Akiba, Hisaya
AU - Takeda, Kazuyoshi
AU - Kojima, Yuko
AU - Hashiguchi, Masaaki
AU - Azuma, Miyuki
AU - Yagita, Hideo
AU - Okumura, Ko
PY - 2009/11/17
Y1 - 2009/11/17
N2 - Phagocytes such as macrophages and dendritic cells (DCs) engulf apoptotic cells to maintain peripheral immune tolerance. However, the mechanism for the recognition of dying cells by phagocytes is not fully understood. Here, we demonstrate that T-cell immunoglobulin mucin-3 (Tim-3) recognizes apoptotic cells through the FG loop in the IgV domain, and is crucial for clearance of apoptotic cells by phagocytes. Whereas Tim-4 is highly expressed on peritoneal resident macrophages, Tim-3 is expressed on peritoneal exudate macrophages, monocytes, and splenic DCs, indicating distinct Tim-mediated phagocytic pathways used by different phagocytes. Furthermore, phagocytosis of apoptotic cells by CD8+ DCs is inhibited by anti-Tim-3 mAb, resulting in a reduced cross-presentation of dying cell-associated antigens in vitro and in vivo. Administration of anti-Tim-3 as well as anti-Tim-4 mAb induces auto-antibody production. These results indicate a crucial role for Tim-3 in phagocytosis of apoptotic cells and cross-presentation, which may be linked to peripheral tolerance.
AB - Phagocytes such as macrophages and dendritic cells (DCs) engulf apoptotic cells to maintain peripheral immune tolerance. However, the mechanism for the recognition of dying cells by phagocytes is not fully understood. Here, we demonstrate that T-cell immunoglobulin mucin-3 (Tim-3) recognizes apoptotic cells through the FG loop in the IgV domain, and is crucial for clearance of apoptotic cells by phagocytes. Whereas Tim-4 is highly expressed on peritoneal resident macrophages, Tim-3 is expressed on peritoneal exudate macrophages, monocytes, and splenic DCs, indicating distinct Tim-mediated phagocytic pathways used by different phagocytes. Furthermore, phagocytosis of apoptotic cells by CD8+ DCs is inhibited by anti-Tim-3 mAb, resulting in a reduced cross-presentation of dying cell-associated antigens in vitro and in vivo. Administration of anti-Tim-3 as well as anti-Tim-4 mAb induces auto-antibody production. These results indicate a crucial role for Tim-3 in phagocytosis of apoptotic cells and cross-presentation, which may be linked to peripheral tolerance.
UR - http://www.scopus.com/inward/record.url?scp=65549168745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65549168745&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-10-185884
DO - 10.1182/blood-2008-10-185884
M3 - Article
C2 - 19224762
AN - SCOPUS:65549168745
VL - 113
SP - 3821
EP - 3830
JO - Blood
JF - Blood
SN - 0006-4971
IS - 16
ER -