Evidence map›Paper›PMID 41480749›Full record

ArticleJCI insight2026

14-3-3ε-dependent deubiquitination and translocation of NLRP3 activates the inflammasome during sepsis.

Xingyu Li, Siqi Ming, Can Cao, Yating Xu, Jingxian Shu, Ning Tan, Xi Huang, Yongjian Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

8 authors.

Xingyu LiCenter for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Siqi MingDepartment of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai Hospital, Zhuhai, Guangdong Province, China.
Can CaoCenter for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Yating XuNational Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, the Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
Jingxian ShuCenter for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Ning TanDepartment of Neonatology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Xi HuangCenter for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Yongjian WuCenter for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The activation of the NLRP3 inflammasome is a pivotal step in hyperinflammation in sepsis; however, the regulatory mechanisms underlying its activation are not fully understood. In this study, we found that 14-3-3ε facilitates NLRP3 inflammasome activation by enhancing NLRP3 K63 deubiquitination and promoting its translocation to the mitochondria-associated ER membranes (MAMs) for full activation. Mass spectrometry revealed that 14-3-3ε binds to NLRP3 in macrophages during sepsis. Plasma 14-3-3ε levels were elevated in patients with sepsis and were positively associated with disease severity. 14-3-3ε promoted NLRP3 inflammasome activation by facilitating NLRP3 aggregation and NLRP3-ASC assembly. The interaction between 14-3-3ε and NLRP3 was dependent on phosphorylation at the S194 site of NLRP3 NACHT domain. The NLRP3-14-3-3ε interaction promoted K63 deubiquitination and enhanced the translocation of NLRP3 to MAMs, which is necessary for full activation of NLRP3 inflammasome. Furthermore, macrophage-conditional KO of 14-3-3ε or treatment with BV02, a 14-3-3 inhibitor, improved the survival rate and alleviated organ injuries in septic mice. Taken together, our data indicate that 14-3-3ε functions as a positive regulator of the NLRP3 inflammasome and could be a target for sepsis treatment.

Indexed as

14-3-3 ProteinsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinSepsisAnimalsFemaleHumansMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutProtein TransportUbiquitination14-3-3 ProteinsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNlrp3 protein, mouseInfectious diseaseInflammationMacrophages

Identifiers

PMID41480749
PMCPMC12890513

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.