Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 5681-5691 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 194 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jun 15 2015 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Immunology
Cite this
DCIR maintains bone homeostasis by regulating IFN-γ production in T cells. / Maruhashi, Takumi; Kaifu, Tomonori; Yabe, Rikio; Seno, Akimasa; Chung, Soo Hyun; Fujikado, Noriyuki; Iwakura, Yoichiro.
In: Journal of Immunology, Vol. 194, No. 12, 15.06.2015, p. 5681-5691.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84931408711&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84931408711&partnerID=8YFLogxK
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 -