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Takumi Maruhashi, Tomonori Kaifu, Rikio Yabe, Akimasa Seno, Soo-Hyun Chung, Noriyuki Fujikado, Yoichiro Iwakura, DCIR Maintains Bone Homeostasis by Regulating IFN-γ Production in T Cells, The Journal of Immunology, Volume 194, Issue 12, June 2015, Pages 5681–5691, https://doi.org/10.4049/jimmunol.1500273
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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.