DCIR in the “osteo-immune” system

Dendritic cell immunoreceptor (Clec4a2, DCIR) is one of C-type lectin receptors (CLRs), which is predominantly expressed in dendritic cells (DCs) [1]. DCIR contains a carbohydrate recognition domain in the extracellular part and an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic region which can negatively regulate immune signaling by recruiting phosphatases, SHP-1 and SHP-2. Previously, Fujikado et al. reported that Dcir-/-mice spontaneously develop autoimmune sialadenitis and enthesitis, that eventually causes ankylotic changes of joints with age [2]. These mice are also highly susceptible to collagen-induced arthritis and experimental autoimmune encephalomyelitis, animal models for rheumatoid arthritis (RA) and multiple sclerosis, respectively. This is because antigen presentation is enhanced in Dcir-/-mice, due to over-expansion of DC population. They showed that Dcir-deficient bone marrow cells differentiate into DCs more efficiently in vitro upon treatment with GM-CSF, because STAT5 activation is augmented in Dcir-/-cells [2]. Thus, DCIR plays an important role in regulating homeostasis of the immune system by regulating DC development and expansion. Recently, Maruhashi and Kaifu et al. investigated the mechanism how joint ankylosis is induced in Dcir-/-mice [3]. They found that not only joint ankylosis but also mild bone volume increase of thigh bones occurs in Dcir-/