Dendritic cell immunoreceptor 1 alters neutrophil responses in the development of experimental colitis.
BACKGROUND
Ulcerative colitis, an inflammatory bowel disease, is associated with the massive infiltration of neutrophils. Although the initial infiltration of neutrophils is beneficial for killing bacteria, it is presumed that persistent infiltration causes tissue damage by releasing antibacterial products as well as inflammatory cytokines. A murine C-type lectin receptor, dendritic cell immunoreceptor 1 (Dcir1), is expressed on CD11b(+) myeloid cells, such as macrophages, dendritic cells and neutrophils. It was reported that Dcir1 is required to maintain homeostasis of the immune system to prevent autoimmunity, but it is also involved in the development of infectious disease resulting in the enhanced severity of cerebral malaria. However, the role of Dcir1 in intestinal immune responses during colitis remains unclear. In this study, we investigated the role of Dcir1 in intestinal inflammation using an experimental colitis model induced with dextran sodium sulfate (DSS).


RESULTS
In contrast to wild type (WT) mice, Dcir1 (-/-) mice exhibited mild body weight loss during the course of DSS colitis accompanied by reduced colonic inflammation. Dcir1 deficiency caused a reduced accumulation of neutrophils in the inflamed colon on day 5 of DSS colitis compared with WT mice. Consistently, the production of a neutrophil-attracting chemokine, MIP-2, was also decreased in the Dcir1 (-/-) colon compared with the WT colon on day 5. There were fewer myeloperoxidase-positive neutrophils in the inflamed colon of Dcir1 (-/-) mice than in that of WT mice. Moreover, bone marrow neutrophils from Dcir1 (-/-) mice produced less reactive oxygen species (ROS) by lipopolysaccharide stimulation than those from WT mice. This suggests that Dcir1 deficiency decreases the accumulation of tissue destructive neutrophils during DSS colitis.


CONCLUSIONS
Dcir1 enhances the pathogenesis of DSS colitis by altering neutrophil recruitment and their functions.
Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, 606-8501, Japan. stokieda.m09@lif.kyoto-u.ac.jp.
Sumika
S
Tokieda
Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, 606-8501, Japan. marie.k@ky2.ecs.kyoto-u.ac.jp.
Marie
M
Komori
Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, 606-8501, Japan. ishiguro.toshifumi.66z@st.kyoto-u.ac.jp.
Toshifumi
T
Ishiguro
Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. iwakura@rs.tus.ac.jp.|Present addresses: Research Institute for Biomedical Sciences, Tokyo University of Science, Yamasaki 2641, Noda, Chiba, 278-0022, Japan. iwakura@rs.tus.ac.jp.
Yoichiro
Y
Iwakura
Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, 606-8501, Japan. ktakahar@zoo.zool.kyoto-u.ac.jp.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan. ktakahar@zoo.zool.kyoto-u.ac.jp.
Kazuhiko
K
Takahara
Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, 606-8501, Japan. kayo@lif.kyoto-u.ac.jp.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan. kayo@lif.kyoto-u.ac.jp.
Kayo
K
Inaba
D000818:Animals; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D003092:Colitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism*; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000235:genetics / Q000276:immunology
D054426:Chemokine CXCL2; D016207:Cytokines; C526731:Dcir protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D016264:Dextran Sulfate; D009195:Peroxidase