TY - JOUR
T1 - Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses
AU - Ohyagi, Hideaki
AU - Onai, Nobuyuki
AU - Sato, Taku
AU - Yotsumoto, Satoshi
AU - Liu, Jiajia
AU - Akiba, Hisaya
AU - Yagita, Hideo
AU - Atarashi, Koji
AU - Honda, Kenya
AU - Roers, Axel
AU - Müller, Werner
AU - Kurabayashi, Kazutaka
AU - Hosoi-Amaike, Mayuka
AU - Takahashi, Naoto
AU - Hirokawa, Makoto
AU - Matsushima, Kouji
AU - Sawada, Kenichi
AU - Ohteki, Toshiaki
N1 - Funding Information:
We thank H. Kamioka for secretarial support, Shoko Kuroda for technical assistance, Nobuhiko Kamada (Keio University) for the B6.Ccl2 −/− mice, Shigekazu Nagata (Kyoto University) for the B6.Mfge8 −/− mice, Dean Sheppard (University of California, San Francisco) for the Ab against integrin α v β 5 , Pamela S. Ohashi (Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University of Toronto, Toronto) for the LCMV Armstrong, and Toshitaka Akatsuka (Saitama Medical University) for the LCMV Clone 13. This work was supported by the Takeda Science Foundation (T.O.), the Joint Usage/Research Program of the Medical Research Institute, Tokyo Medical and Dental University (K.S.), a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan (T.O.), Challenging Exploratory Research (T.O.), and Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST) (T.O.).
PY - 2013/9/19
Y1 - 2013/9/19
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2013.06.019
DO - 10.1016/j.immuni.2013.06.019
M3 - Article
C2 - 24035363
AN - SCOPUS:84884344619
SN - 1074-7613
VL - 39
SP - 584
EP - 598
JO - Immunity
JF - Immunity
IS - 3
ER -
