Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells.
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.
Fujikado
Noriyuki
N
Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Saijo
Shinobu
S
Yonezawa
Tomo
T
Shimamori
Kazusuke
K
Ishii
Akina
A
Sugai
Sho
S
Kotaki
Hayato
H
Sudo
Katsuko
K
Nose
Masato
M
Iwakura
Yoichiro
Y
D000375:Aging / Q000187:drug effects; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology*; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D037181:Lectins, C-Type / Q000172:deficiency*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
C526731:Dcir protein, mouse; D037181:Lectins, C-Type; D016178:Granulocyte-Macrophage Colony-Stimulating Factor