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

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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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ASJC Scopus subject areas

  • Immunology and Allergy
  • 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