title: Absence of DCIR1 reduces the mortality rate of endotoxemic hepatitis in mice.
abstract: Dendritic cell immunoreceptor (DCIR) is a C-type lectin with an immunoreceptor tyrosine-based inhibitory motif (ITIM). Mice lacking DCIR1 (Dcir1-/-mice) show higher susceptibility to chronic arthritis with increasing age, suggesting that DCIR1 is involved in immune modulation via its ITIM. However, the role of DCIR1 in acute immune responses is not clear. In this study, we explored its role in acute experimental hepatitis. Upon injection of d-galactosamine and lipopolysaccharide, Dcir1-/-mice showed decreased mortality rates and serum levels of alanine aminotransferase. In early onset hepatitis, serum levels of TNF-α, which primarily cause inflammation and hepatocyte apoptosis, were significantly lower in Dcir1-/-mice than in WT mice. In the liver of Dcir1-/-mice, influx of neutrophils and other leukocytes decreased. Consistently, the levels of neutrophil-chemoattractant chemokine CXCL1/KC, but not CXCL2/MIP-2, were lower in Dcir1-/-mice than in WT mice. However, chemotaxis of Dcir1-/-neutrophils to CXCL1/KC appeared normal. Pervanadate treatment induced binding of DCIR1 and Src homology region 2 domain-containing phosphatase (SHP)-2, possibly leading to CXCL1/KC expression. These results suggest that DCIR1 is involved in exacerbation of endotoxemic hepatitis, providing a new therapeutic target for lethal hepatitis.
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ishiguro
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukawa
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Akaki
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagaoka
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.affiliation: Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahara
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D019446:Endotoxemia / Q000188:drug therapy / Q000276:immunology*; D005688:Galactosamine / Q000008:administration & dosage; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D009504:Neutrophils / Q000276:immunology*; D014638:Vanadates / Q000494:pharmacology
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C526731:Dcir protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; C076715:pervanadate; D014638:Vanadates; D005688:Galactosamine
keywords: C-type lectin; Chemokine; Dendritic cell immunoreceptor; Hepatitis; Neutrophil; SHP-2