Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study
Abstract Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis pa...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56524-3 |
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| author | Taylor Roh Sungeun Ju So Young Park Yeonghwan Ahn Jiyun Chung Miyako Nakano Gyoungah Ryu Young Jae Kim Geumseo Kim Hyewon Choi Sung-Gwon Lee In Soo Kim Song-I Lee Chaeuk Chung Takashi Shimizu Eiji Miyoshi Sung-Soo Jung Chungoo Park Sho Yamasaki Seung-Yeol Park Eun-Kyeong Jo |
| author_facet | Taylor Roh Sungeun Ju So Young Park Yeonghwan Ahn Jiyun Chung Miyako Nakano Gyoungah Ryu Young Jae Kim Geumseo Kim Hyewon Choi Sung-Gwon Lee In Soo Kim Song-I Lee Chaeuk Chung Takashi Shimizu Eiji Miyoshi Sung-Soo Jung Chungoo Park Sho Yamasaki Seung-Yeol Park Eun-Kyeong Jo |
| author_sort | Taylor Roh |
| collection | DOAJ |
| description | Abstract Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FUT4 in response to Fu-Hp. Additionally, Mincle, a C-type lectin receptor, interacts with Fu-Hp to amplify the inflammatory responses and signaling. Moreover, the Hp fucosylation (AAL) level significantly correlates with the levels of inflammatory cytokines in sepsis patients, suggesting that Fu-Hp is clinically relevant. Finally, Fu-Hp treatment significantly enhances the levels of inflammatory cytokines in the plasma and various tissues of mice. Together, our findings reveal a role of Fu-Hp, derived from sepsis patients, in driving inflammation, and suggest that targeting Fu-Hp could serve as a promising intervention for combating sepsis. Trial registration NCT05911711 |
| format | Article |
| id | doaj-art-87d3b37c6d374223a7a9345e830b9270 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-87d3b37c6d374223a7a9345e830b92702025-02-09T12:45:42ZengNature PortfolioNature Communications2041-17232025-02-0116112110.1038/s41467-025-56524-3Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational studyTaylor Roh0Sungeun Ju1So Young Park2Yeonghwan Ahn3Jiyun Chung4Miyako Nakano5Gyoungah Ryu6Young Jae Kim7Geumseo Kim8Hyewon Choi9Sung-Gwon Lee10In Soo Kim11Song-I Lee12Chaeuk Chung13Takashi Shimizu14Eiji Miyoshi15Sung-Soo Jung16Chungoo Park17Sho Yamasaki18Seung-Yeol Park19Eun-Kyeong Jo20Department of Microbiology, College of Medicine, Chungnam National UniversityDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH)Division of Pulmonary, Allergy and Critical Care Medicine, Kangdong Sacred Heart HospitalDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH)Department of Life Sciences, Pohang University of Science and Technology (POSTECH)Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-HiroshimaDepartment of Microbiology, College of Medicine, Chungnam National UniversityDepartment of Microbiology, College of Medicine, Chungnam National UniversityDepartment of Microbiology, College of Medicine, Chungnam National UniversityDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH)Section of Genetics and Physiology, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)Department of Medical Science, College of Medicine, Chungnam National UniversityDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University HospitalDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National UniversityDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, SuitaDepartment of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka University, SuitaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National UniversitySchool of Biological Sciences and Technology, Chonnam National UniversityDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, SuitaDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH)Department of Microbiology, College of Medicine, Chungnam National UniversityAbstract Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FUT4 in response to Fu-Hp. Additionally, Mincle, a C-type lectin receptor, interacts with Fu-Hp to amplify the inflammatory responses and signaling. Moreover, the Hp fucosylation (AAL) level significantly correlates with the levels of inflammatory cytokines in sepsis patients, suggesting that Fu-Hp is clinically relevant. Finally, Fu-Hp treatment significantly enhances the levels of inflammatory cytokines in the plasma and various tissues of mice. Together, our findings reveal a role of Fu-Hp, derived from sepsis patients, in driving inflammation, and suggest that targeting Fu-Hp could serve as a promising intervention for combating sepsis. Trial registration NCT05911711https://doi.org/10.1038/s41467-025-56524-3 |
| spellingShingle | Taylor Roh Sungeun Ju So Young Park Yeonghwan Ahn Jiyun Chung Miyako Nakano Gyoungah Ryu Young Jae Kim Geumseo Kim Hyewon Choi Sung-Gwon Lee In Soo Kim Song-I Lee Chaeuk Chung Takashi Shimizu Eiji Miyoshi Sung-Soo Jung Chungoo Park Sho Yamasaki Seung-Yeol Park Eun-Kyeong Jo Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study Nature Communications |
| title | Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study |
| title_full | Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study |
| title_fullStr | Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study |
| title_full_unstemmed | Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study |
| title_short | Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study |
| title_sort | fucosylated haptoglobin promotes inflammation via mincle in sepsis an observational study |
| url | https://doi.org/10.1038/s41467-025-56524-3 |
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