ID: 226: DCIR maintains bone homeostasis by regulating IFN-γ production in T cells

Abstract

Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor with a canonical signal motif for initiating inhibitory signals in the cytoplasmic region. In accordance with the structural insights, Dcir−/− mice spontaneously developed autoimmune-like diseases like sialadenitis and swelling and redness of joints. Thus, DCIR is a pivotal regulator for maintaining the homeostasis of the immune system. Furthermore, Dcir−/− mice not only developed ankylosis, characterized by aberrant cartilage and bone formation, but also increased bone volume, accompanied with the higher number of osteoclasts and osteoblasts (OBs). To understand the role of DCIR in bone metabolism, we dissected the molecular mechanism affecting the bone volume in Dcir−/− mice. Flow cytometry analyses revealed that Dcir−/− mice increased IFN- γ -positive T cells in peripheral blood and lymph nodes. Dcir−/− dendritic cells had higher potency to shape IFN- γ -positive T cells in the co-culture with wild-type T cells. X-ray histomorphometric analysis revealed that both Rag2−/− Dcir−/− and Ifng−/− Dcir−/− negated the increase of bone volume, suggesting that T cell-secreting IFN- γ be a pathogenic in the increased bone mass. In in vitro OB culture system, we identified IFN- γ as an osteogenic factor capable of facilitating mineralization of OBs, indicating that IFN- γ released from T cells acts on OBs. These findings demonstrate that Dcir−/− mice had increased IFN- γ -positive T cells, which accelerates mineralization of OBs, leading to the increased bone volume. Collectively, DCIR plays a key role in maintaining bone homeostasis and IFN- γ functions as an enhancing factor in bone formation.