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DCIR及其配体去唾液酸双触角N-聚糖调节树突状细胞功能和破骨细胞生成。

DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis.

作者信息

Kaifu Tomonori, Yabe Rikio, Maruhashi Takumi, Chung Soo-Hyun, Tateno Hiroaki, Fujikado Noriyuki, Hirabayashi Jun, Iwakura Yoichiro

机构信息

Center for Animal Disease Models, Research Institution for Biological Sciences, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan.

Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan.

出版信息

J Exp Med. 2021 Dec 6;218(12). doi: 10.1084/jem.20210435. Epub 2021 Nov 24.

DOI:10.1084/jem.20210435
PMID:34817551
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8624811/
Abstract

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.

摘要

树突状细胞免疫受体（DCIR）是一种C型凝集素受体，具有碳水化合物识别结构域和基于免疫受体酪氨酸的抑制基序。此前，我们发现Dcir-/-小鼠会自发发展为自身免疫性附着点炎和涎腺炎，还会出现代谢性骨异常。然而，DCIR功能的配体仍有待阐明。在此我们发现，DCIR在破骨细胞和树突状细胞上表达，并与骨细胞和髓样细胞上的去唾液酸双触角N-聚糖（NA2）结合。在Dcir-/-细胞中破骨细胞生成增强，而NA2抑制破骨细胞生成。神经氨酸酶处理通过去除N-聚糖的末端唾液酸使过量的NA2暴露，从而抑制破骨细胞生成和树突状细胞功能。对小鼠进行神经氨酸酶处理以DCIR依赖的方式改善了胶原诱导的关节炎和实验性自身免疫性脑脊髓炎，这是由于树突状细胞对抗原呈递的抑制作用。这些结果表明，DCIR的活性受双触角N-聚糖末端唾液酸化修饰的调节，并且这种相互作用对于自身免疫性疾病和骨代谢疾病的控制都很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0221/8624811/d619093c8b9d/JEM_20210435_FigS5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0221/8624811/df3678cb9e7b/JEM_20210435_FigS1.jpg
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