TY - JOUR
T1 - DCIR maintains bone homeostasis by regulating IFN-γ production in T cells
AU - Maruhashi, Takumi
AU - Kaifu, Tomonori
AU - Yabe, Rikio
AU - Seno, Akimasa
AU - Chung, Soo Hyun
AU - Fujikado, Noriyuki
AU - Iwakura, Yoichiro
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/6/15
Y1 - 2015/6/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1500273
DO - 10.4049/jimmunol.1500273
M3 - Article
C2 - 25926676
AN - SCOPUS:84931408711
VL - 194
SP - 5681
EP - 5691
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -