DCIR maintains bone homeostasis by regulating IFN-γ production in T cells

Takumi Maruhashi, Tomonori Kaifu, Rikio Yabe, Akimasa Seno, Soo Hyun Chung, Noriyuki Fujikado, Yoichiro Iwakura

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish
Pages (from-to)5681-5691
Number of pages11
JournalJournal of Immunology
Volume194
Issue number12
DOIs
Publication statusPublished - Jun 15 2015
Externally publishedYes

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Dendritic Cells
Homeostasis
T-Lymphocytes
Bone and Bones
Osteogenesis
Joints
Fibrocartilage
C-Type Lectins
Heterotopic Ossification
Ankylosis
Metabolic Bone Diseases
Femur
Cartilage
Cell Differentiation
Lymph Nodes
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Maruhashi, T., Kaifu, T., Yabe, R., Seno, A., Chung, S. H., Fujikado, N., & Iwakura, Y. (2015). DCIR maintains bone homeostasis by regulating IFN-γ production in T cells. Journal of Immunology, 194(12), 5681-5691. https://doi.org/10.4049/jimmunol.1500273

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 journalArticle

Maruhashi, T, Kaifu, T, Yabe, R, Seno, A, Chung, SH, Fujikado, N & Iwakura, Y 2015, 'DCIR maintains bone homeostasis by regulating IFN-γ production in T cells', Journal of Immunology, vol. 194, no. 12, pp. 5681-5691. https://doi.org/10.4049/jimmunol.1500273
Maruhashi, Takumi ; Kaifu, Tomonori ; Yabe, Rikio ; Seno, Akimasa ; Chung, Soo Hyun ; Fujikado, Noriyuki ; Iwakura, Yoichiro. / DCIR maintains bone homeostasis by regulating IFN-γ production in T cells. In: Journal of Immunology. 2015 ; Vol. 194, No. 12. pp. 5681-5691.
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