@article{385ffe26531f4fb79e46ca40f2af2744,
title = "Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2",
abstract = "C-type lectin receptors (CLRs) elicit immune responses upon recognition of glycocon-jugates present on pathogens and self-components. While Dectin-1 is the best-characterized CLR recognizing β-glucan on pathogens, the endogenous targets of Dectin-1 are not fully understood. Herein, we report that human Dectin-1 is a ligand for CLEC-2, another CLR expressed on plate-lets. Biochemical analyses revealed that Dectin-1 is a mucin-like protein as its stalk region is highly O-glycosylated. A sialylated core 1 glycan attached to the EDxxT motif of human Dectin-1, which is absent in mouse Dectin-1, provides a ligand moiety for CLEC-2. Strikingly, the expression of human Dectin-1 in mice rescued the lethality and lymphatic defect resulting from a deficiency of Podo-planin, a known CLEC-2 ligand. This finding is the first example of an innate immune receptor also functioning as a physiological ligand to regulate ontogeny upon glycosylation.",
author = "Shojiro Haji and Taiki Ito and Carla Guenther and Miyako Nakano and Takashi Shimizu and Daiki Mori and Yasunori Chiba and Masato Tanaka and Mishra, {Sushil K.} and Willment, {Janet A.} and Brown, {Gordon D.} and Masamichi Nagae and Sho Yamasaki",
note = "Funding Information: The authors are grateful to D Motooka, S Iwai, F Sugihara, K Kaseda, M Ikawa, H Shimizu, K Matoba, W Okawa, and D Murai for technical support; M Netea, Y Kizuka, Y Yamaguchi, N Taniguchi, J Takagi, and Y Ogawa for discussion. The authors also thank the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University, the NGS core facility of Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University for their technical support. This work was supported by JSPS KAKENHI Grant numbers JP 16H06276 (AdAMS), 20H00505, 20K06575, and 22H05183 and by the Grant for Joint Research Project of the Research Institute for Microbial Diseases, and IFReC Kishimoto Foundation Fellowship, Osaka University. Publisher Copyright: {\textcopyright} Haji et al.",
year = "2022",
month = dec,
doi = "10.7554/ELIFE.83037",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}