Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

Shojiro Haji; Taiki Ito; Carla Guenther; Miyako Nakano; Takashi Shimizu; Daiki Mori; Yasunori Chiba; Masato Tanaka; Sushil K. Mishra; Janet A. Willment; Gordon D. Brown; Masamichi Nagae; Sho Yamasaki

doi:10.7554/ELIFE.83037

Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

Shojiro Haji, Taiki Ito, Carla Guenther, Miyako Nakano, Takashi Shimizu, Daiki Mori, Yasunori Chiba, Masato Tanaka, Sushil K. Mishra, Janet A. Willment, Gordon D. Brown, Masamichi Nagae, Sho Yamasaki

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e83037
Journal	eLife
Volume	11
DOIs	https://doi.org/10.7554/ELIFE.83037
Publication status	Published - Dec 2022
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

Access to Document

10.7554/ELIFE.83037

Cite this

@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",

}

TY - JOUR

T1 - Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

AU - Haji, Shojiro

AU - Ito, Taiki

AU - Guenther, Carla

AU - Nakano, Miyako

AU - Shimizu, Takashi

AU - Mori, Daiki

AU - Chiba, Yasunori

AU - Tanaka, Masato

AU - Mishra, Sushil K.

AU - Willment, Janet A.

AU - Brown, Gordon D.

AU - Nagae, Masamichi

AU - Yamasaki, Sho

N1 - 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: © Haji et al.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85144637107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85144637107&partnerID=8YFLogxK

U2 - 10.7554/ELIFE.83037

DO - 10.7554/ELIFE.83037

M3 - Article

C2 - 36479973

AN - SCOPUS:85144637107

SN - 2050-084X

VL - 11

JO - eLife

JF - eLife

M1 - e83037

ER -

Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this