DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling

Dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lectin receptor that acts as a negative regulator in the immune system and bone metabolism. We previously revealed that DCIR deficiency enhanced osteoclastogenesis and antigen presentation of dendritic cells, and that asialo-biantennary N-...

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Bibliographic Details
Published in:Frontiers in immunology 2023-05, Vol.14, p.1159058-1159058
Main Authors: Kaifu, Tomonori, Maruhashi, Takumi, Chung, Soo-Hyun, Shimizu, Kenji, Nakamura, Akira, Iwakura, Yoichiro
Format: Article
Language:English
Subjects:
Animals
Bone Resorption - metabolism
C-type lectin receptor
Cell Proliferation
cytokines
homeostasis
Humans
Immunology
Macrophage Colony-Stimulating Factor - metabolism
Macrophage Colony-Stimulating Factor - pharmacology
metabolism
Mice
oligosaccharides
osteoclast
Osteoclasts - metabolism
Signal Transduction
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Summary:Dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lectin receptor that acts as a negative regulator in the immune system and bone metabolism. We previously revealed that DCIR deficiency enhanced osteoclastogenesis and antigen presentation of dendritic cells, and that asialo-biantennary N-glycan (NA2) functions as a ligand for DCIR. NA2 binding to DCIR suppressed murine and human osteoclastogenesis that occurs in the presence of M-CSF and RANKL. The DCIR-NA2 axis, therefore, plays an important role in regulating osteoclastogenesis in both mice and humans, although the underlying mechanisms remain unclear. Here we found that bone marrow-derived macrophages (BMMs) exhibited greater proliferative and differentiation responses to M-CSF and RANKL, respectively, than wild-type (WT) BMMs. Moreover, osteoclasts (OCs) increased resorptive activity and cell fusion more significantly than WT OCs. DCIR deficiency affects gene expression patterns in OCs, and we found that the expression of neuraminidase 4 was increased in OCs. Furthermore, DCIR-NA2 interaction in WT BMMs, but not BMMs, decreased Akt phosphorylation in response to M-CSF and RANKL. These data suggest that DCIR regulates osteoclastogenesis by downregulating M-CSF and RANKL signaling, and that DCIR-mediated signaling may contribute to the terminal modification of oligosaccharides by controlling the expression of glycosylation enzymes.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1159058