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KIM ‐1‐/ TIM ‐1‐mediated phagocytosis links ATG 5‐/ ULK 1‐dependent clearance of apoptotic cells to antigen presentation
Author(s) -
Brooks Craig R,
Yeung Melissa Y,
Brooks Yang S,
Chen Hui,
Ichimura Takaharu,
Henderson Joel M,
Bonventre Joseph V
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489838
Subject(s) - phagocytosis , phagosome , autophagy , microbiology and biotechnology , biology , antigen presentation , apoptosis , immune system , t cell , immunology , biochemistry
Phagocytosis of apoptotic cells by both professional and semi‐professional phagocytes is required for resolution of organ damage and maintenance of immune tolerance. KIM ‐1/ TIM ‐1 is a phosphatidylserine receptor that is expressed on epithelial cells and can transform the cells into phagocytes. Here, we demonstrate that KIM ‐1 phosphorylation and association with p85 results in encapsulation of phagosomes by lipidated LC 3 in multi‐membrane organelles. KIM ‐1‐mediated phagocytosis is not associated with increased ROS production, and NOX inhibition does not block LC 3 lipidation. Autophagy gene expression is required for efficient clearance of apoptotic cells and phagosome maturation. KIM ‐1‐mediated phagocytosis leads to pro‐tolerogenic antigen presentation, which suppresses CD 4 T‐cell proliferation and increases the percentage of regulatory T cells in an autophagy gene‐dependent manner. Taken together, these data reveal a novel mechanism of epithelial biology linking phagocytosis, autophagy and antigen presentation to regulation of the inflammatory response.