Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses

Hideaki Ohyagi, Nobuyuki Onai, Taku Sato, Satoshi Yotsumoto, Jiajia Liu, Hisaya Akiba, Hideo Yagita, Koji Atarashi, Kenya Honda, Axel Roers, Werner Müller, Kazutaka Kurabayashi, Mayuka Hosoi-Amaike, Naoto Takahashi, Makoto Hirokawa, Kouji Matsushima, Kenichi Sawada, Toshiaki Ohteki

研究成果: Article査読

50 被引用数 (Scopus)

抄録

Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic Tcell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival invivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.

本文言語English
ページ(範囲)584-598
ページ数15
ジャーナルImmunity
39
3
DOI
出版ステータスPublished - 2013 9 19
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 感染症

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