Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation

Masafumi Nakayama, Hisaya Akiba, Kazuyoshi Takeda, Yuko Kojima, Masaaki Hashiguchi, Miyuki Azuma, Hideo Yagita, Ko Okumura

Research output: Contribution to journalArticlepeer-review

242 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3821-3830
Number of pages10
JournalBlood
Volume113
Issue number16
DOIs
Publication statusPublished - 2009 Nov 17

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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