IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56524-3.html
   My bibliography  Save this article

Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study

Author

Listed:
  • Taylor Roh

    (Chungnam National University
    Chungnam National University
    Chungnam National University)

  • Sungeun Ju

    (Pohang University of Science and Technology (POSTECH))

  • So Young Park

    (Kangdong Sacred Heart Hospital)

  • Yeonghwan Ahn

    (Pohang University of Science and Technology (POSTECH))

  • Jiyun Chung

    (Pohang University of Science and Technology (POSTECH))

  • Miyako Nakano

    (Higashi-Hiroshima)

  • Gyoungah Ryu

    (Chungnam National University
    Chungnam National University)

  • Young Jae Kim

    (Chungnam National University
    Chungnam National University
    Chungnam National University)

  • Geumseo Kim

    (Chungnam National University
    Chungnam National University
    Chungnam National University)

  • Hyewon Choi

    (Pohang University of Science and Technology (POSTECH))

  • Sung-Gwon Lee

    (National Institutes of Health (NIH))

  • In Soo Kim

    (Chungnam National University
    Chungnam National University
    Chungnam National University)

  • Song-I Lee

    (Chungnam National University Hospital)

  • Chaeuk Chung

    (Chungnam National University)

  • Takashi Shimizu

    (Suita
    Suita)

  • Eiji Miyoshi

    (Suita)

  • Sung-Soo Jung

    (Chungnam National University)

  • Chungoo Park

    (Chonnam National University)

  • Sho Yamasaki

    (Suita
    Suita
    Suita)

  • Seung-Yeol Park

    (Pohang University of Science and Technology (POSTECH))

  • Eun-Kyeong Jo

    (Chungnam National University
    Chungnam National University)

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

Suggested Citation

  • 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 Chun, 2025. "Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56524-3
    DOI: 10.1038/s41467-025-56524-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56524-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56524-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mette Kristiansen & Jonas H. Graversen & Christian Jacobsen & Ole Sonne & Hans-Jürgen Hoffman & S.K. Alex Law & Søren K. Moestrup, 2001. "Identification of the haemoglobin scavenger receptor," Nature, Nature, vol. 409(6817), pages 198-201, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Magdalena Mierzchała-Pasierb & Małgorzata Lipińska-Gediga & Łukasz Lewandowski & Małgorzata Krzystek-Korpacka, 2023. "Alterations in Serum Concentration of Soluble CD163 within Five Study Days from ICU Admission Are Associated with In-Hospital Mortality of Septic Patients—A Preliminary Study," IJERPH, MDPI, vol. 20(3), pages 1-21, January.
    2. Anders Etzerodt & Jakob Hauge Mikkelsen & Morten Torvund-Jensen & Dorle Hennig & Thomas Boesen & Jonas Heilskov Graversen & Søren Kragh Moestrup & Justin M. Kollman & Christian Brix Folsted Andersen, 2024. "The Cryo-EM structure of human CD163 bound to haptoglobin-hemoglobin reveals molecular mechanisms of hemoglobin scavenging," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Eric D. Morrell & Sarah E. Holton & Matthew Lawrance & Marika Orlov & Zoie Franklin & Mallorie A. Mitchem & Hannah DeBerg & Vivian H. Gersuk & Ashley Garay & Elizabeth Barnes & Ted Liu & Ithan D. Pelt, 2023. "The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56524-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.