PMID- 18204462
OWN - NLM
STAT- MEDLINE
DCOM- 20080225
LR  - 20080207
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 14
IP  - 2
DP  - 2008 Feb
TI  - Dcir deficiency causes development of autoimmune diseases in mice due to excess 
      expansion of dendritic cells.
PG  - 176-80
LID - 10.1038/nm1697 [doi]
AB  - The dendritic cell immunoreceptor (official gene symbol Clec4a2, called Dcir 
      here) is a C-type lectin receptor expressed mainly in dendritic cells (DCs) that 
      has a carbohydrate recognition domain in its extracellular portion and an 
      immunoreceptor tyrosine-based inhibitory motif, which transduces negative signals 
      into cells, in its cytoplasmic portion. We found high Dcir expression in the 
      joints of two mouse rheumatoid arthritis models. Because the structural 
      characteristics of Dcir suggest that it may have an immune regulatory role, and 
      because autoimmune-related genes are mapped to the DCIR locus in humans, we 
      generated Dcir-/- mice to learn more about the pathological roles of this 
      molecule. We found that aged Dcir-/- mice spontaneously develop sialadenitis and 
      enthesitis associated with elevated serum autoantibodies. Dcir-/- mice showed a 
      markedly exacerbated response to collagen-induced arthritis. The DC population 
      was expanded excessively in aged and type II collagen-immunized Dcir-/- mice. 
      Upon treatment with granulocyte-macrophage colony-stimulating factor, Dcir-/- 
      mouse-derived bone marrow cells (BMCs) differentiated into DCs more efficiently 
      than did wild-type BMCs, owing to enhanced signal transducer and activator of 
      transcription-5 phosphorylation. These observations indicate that Dcir is a 
      negative regulator of DC expansion and has a crucial role in maintaining the 
      homeostasis of the immune system.
FAU - Fujikado, Noriyuki
AU  - Fujikado N
AD  - Center for Experimental Medicine, The Institute of Medical Science, The 
      University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
FAU - Saijo, Shinobu
AU  - Saijo S
FAU - Yonezawa, Tomo
AU  - Yonezawa T
FAU - Shimamori, Kazusuke
AU  - Shimamori K
FAU - Ishii, Akina
AU  - Ishii A
FAU - Sugai, Sho
AU  - Sugai S
FAU - Kotaki, Hayato
AU  - Kotaki H
FAU - Sudo, Katsuko
AU  - Sudo K
FAU - Nose, Masato
AU  - Nose M
FAU - Iwakura, Yoichiro
AU  - Iwakura Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080120
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Dcir protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Aging/drug effects
MH  - Animals
MH  - Arthritis, Experimental/immunology/pathology
MH  - Autoimmune Diseases/*immunology/*pathology
MH  - Autoimmunity/drug effects/immunology
MH  - Bone Marrow Cells/drug effects
MH  - Cell Proliferation/drug effects
MH  - Dendritic Cells/*cytology/drug effects/*immunology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Lectins, C-Type/*deficiency
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - T-Lymphocytes/drug effects/immunology
EDAT- 2008/01/22 09:00
MHDA- 2008/02/26 09:00
CRDT- 2008/01/22 09:00
PHST- 2007/10/24 00:00 [received]
PHST- 2007/11/29 00:00 [accepted]
PHST- 2008/01/22 09:00 [pubmed]
PHST- 2008/02/26 09:00 [medline]
PHST- 2008/01/22 09:00 [entrez]
AID - nm1697 [pii]
AID - 10.1038/nm1697 [doi]
PST - ppublish
SO  - Nat Med. 2008 Feb;14(2):176-80. doi: 10.1038/nm1697. Epub 2008 Jan 20.