DCIR maintains bone homeostasis by regulating IFN-γ production in T cells.
Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor mainly expressed in DCs. Dcir (-/-) mice spontaneously develop autoimmune enthesitis and ankylosis accompanied by fibrocartilage proliferation and ectopic ossification. However, the mechanisms of new bone/cartilage formation in Dcir (-/-) mice remain to be elucidated. In this study, we show that DCIR maintains bone homeostasis by regulating IFN-γ production under pathophysiological conditions. DCIR deficiency increased bone volume in femurs and caused aberrant ossification in joints, whereas these symptoms were abolished in Rag2(-/-)Dcir(-/-) mice. IFN-γ-producing T cells accumulated in lymph nodes and joints of Dcir(-/-) mice, and purified Dcir(-/-) DCs enhanced IFN-γ(+) T cell differentiation. The ankylotic changes and bone volume increase were suppressed in the absence of IFN-γ. Thus, IFN-γ is a positive chondrogenic and osteoblastogenic factor, and DCIR is a crucial regulator of bone metabolism; consequently, both factors are potential targets for therapies directed against bone metabolic diseases.
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan;
Takumi
T
Maruhashi
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; and.
Tomonori
T
Kaifu
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan; Medical Mycology Research Center, Chiba University, Chiba 250-8673, Japan.
Rikio
R
Yabe
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Medical Mycology Research Center, Chiba University, Chiba 250-8673, Japan.
Akimasa
A
Seno
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan;
Soo-Hyun
SH
Chung
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; and.
Noriyuki
N
Fujikado
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; and Medical Mycology Research Center, Chiba University, Chiba 250-8673, Japan iwakura@rs.tus.ac.jp.
Yoichiro
Y
Iwakura
D000367:Age Factors; D000818:Animals; D000844:Ankylosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015519:Bone Density / Q000235:genetics; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics* / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D055114:X-Ray Microtomography
D004268:DNA-Binding Proteins; C526731:Dcir protein, mouse; D037181:Lectins, C-Type; C499308:Rag2 protein, mouse; D007371:Interferon-gamma