Evidence map›Paper›PMID 35921817›Full record

ArticleCell metabolism2022

CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder.

Xu Wang, Mingyue Liu, Jifeng Zhang, Nicholas K Brown, Peng Zhang, Yan Zhang, Heng Liu, Xuexiang Du, Wei Wu, Martin Devenport and 6 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02650895 (A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of CD24Fc When Administered Intravenously in Healthy Adult Subjects), which is not on this map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02650895 phase1completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of CD24Fc When Administered Intravenously in Healthy Adult Subjects

TypeinterventionalSponsorOncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Ran2014 to 2015Enrolled40ConditionsHealthy VolunteersArmsEfprezimod alfa, Saline
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 58 citations in OpenAlex.

  1. Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Xu WangDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mingyue LiuDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jifeng ZhangDepartment of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
Nicholas K BrownDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Peng ZhangDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Yan ZhangDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Heng LiuDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Xuexiang DuDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Key Laboratory of Infection and Immunity of Shandong Province & Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China.
Wei WuDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
Martin DevenportOncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
Weng TaoOncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
Yang Mao-DraayerDepartment of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
Guo-Yun ChenChildren's Foundation Research Institute, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Y Eugene ChenDepartment of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
Pan ZhengDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA. Electronic address: pzheng@oncoc4.com.
Yang LiuDivision of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA. Electronic address: yangl@oncoc4.com.
University of Maryland, Baltimore · USUniversity of Michigan · USOncoceutics (United States) · USUniversity of Pennsylvania · USUniversity of Tennessee Health Science Center · US

Funding

Checkpoints of Host Response to Cellular InjuriesR01AI064350 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, YANG, ZHENG, PAN · 2006 to 2019
$5.6M
A Mouse Model to Assess Long Term Immunotherapy-related Adverse Effects in ChildrenR01CA227671 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI WANG, YIN · 2018 to 2022
$2.1M
Targeting Siglec-9/E for therapy of sepsisR01AI137255 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI CHEN, GUOYUN · 2018 to 2022
$1.9M
CD24 Targeting for Multiple Sclerosis: a First-In-Human Phase I StudyR01NS080821 · NINDS · ONCOIMMUNE, INC. · PI LIU, YANG · 2013 to 2014
$1.1M
NCI NIH HHS R01 CA227671NIAID NIH HHS R01 AI064350NIAID NIH HHS R01 AI137255NINDS NIH HHS R01 NS080821
6 · The paper itself

Abstract

The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.

Indexed as

Metabolic DiseasesSialic Acid Binding Immunoglobulin-like LectinsAnimalsCD24 AntigenClinical Studies as TopicHumansInflammationMiceObesityPhagocytosisCD24 AntigenCD24 protein, humanSialic Acid Binding Immunoglobulin-like LectinsCD24insulin resistancemetabolic syndromemetaflammationNASHobesitysialic acid-binding immunoglobulin-like lectinssialylationSiglec-ESiglecs

Identifiers

PMID35921817
PMCPMC9393047
OpenAlexW4289525498

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.