Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor with a carbohydrate recognition domain and an immunoreceptor tyrosine-based inhibitory motif. Previously, we showed that Dcir−/− mice spontaneously develop autoimmune enthesitis and sialadenitis, and also develop metabolic bone abnormalities. However, the ligands for DCIR functionality remain to be elucidated. Here we showed that DCIR is expressed on osteoclasts and DCs and binds to an asialo-biantennary N-glycan(s) (NA2) on bone cells and myeloid cells. Osteoclastogenesis was enhanced in Dcir−/− cells, and NA2 inhibited osteoclastogenesis. Neuraminidase treatment, which exposes excess NA2 by removing the terminal sialic acid of N-glycans, suppressed osteoclastogenesis and DC function. Neuraminidase treatment of mice ameliorated collagen-induced arthritis and experimental autoimmune encephalomyelitis in a DCIR-dependent manner, due to suppression of antigen presentation by DCs. These results suggest that DCIR activity is regulated by the modification of the terminal sialylation of biantennary N-glycans, and this interaction is important for the control of both autoimmune and bone metabolic diseases.
DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis
Disclosures: T. Kaifu and Y. Iwakura reported a patent to 6674685 (Japan) issued, a patent to 10,792,300 (USA) issued, and a patent to PCT/JP2018/018610 pending. No other disclosures were reported.
T. Kaifu’s present address is Division of Immunology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Fukumuro, Miyaginoku, Sendai, Miyagi, Japan.
R. Yabe’s present address is Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
T. Maruhashi’s present address is Laboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan.
N. Fujikado’s present address is Lilly Research Laboratories, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA.
J. Hirabayashi’s present address is Tokai National Higher Education and Research System, Nagoya University, Tsurumai-cho, Show-ku, Nagoya, Japan.
- Award Id(s): 105100000222
- Award Id(s): 24220011,20H04954
- Award Id(s): 16809407
- Award Id(s): 23500489
- Views Icon Views
- Share Icon Share
- Search Site
Tomonori Kaifu, Rikio Yabe, Takumi Maruhashi, Soo-Hyun Chung, Hiroaki Tateno, Noriyuki Fujikado, Jun Hirabayashi, Yoichiro Iwakura; DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis. J Exp Med 6 December 2021; 218 (12): e20210435. doi: https://doi.org/10.1084/jem.20210435
Download citation file: