Evidence map›Paper›PMID 36426349›Full record

ArticleFrontiers in immunology2022

The CARD8 T60 variant associates with NLRP1 and negatively regulates its activation.

Zhihao Xu, Shasha Deng, Yuluo Huang, Yunru Yang, Liangqi Sun, Hanyuan Liu, Dan Zhao, Weihong Zeng, Xueying Yin, Peiyi Zheng and 6 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 44% 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.

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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. NLRP inflammasomes in health and disease.Molecular biomedicine · 2024
    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

16 authors at 3 institutions in 2 countries.

Zhihao XuDepartment of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Shasha DengLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Yuluo HuangLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Yunru YangLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Liangqi SunLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Hanyuan LiuDepartment of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Dan ZhaoLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Weihong ZengLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Xueying YinLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Peiyi ZhengLaboratory of Structural Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Yingying WangDepartment of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Muziying LiuAnhui Institute of Pediatric Research, Anhui Provincial Children's Hospital, Hefei, China.
Weidong ZhaoDepartment of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Tsan Sam XiaoDepartment of Pathology, Case Western Reserve University, Cleveland, OH, United States.
Ying ZhouDepartment of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Tengchuan JinDepartment of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
University of Science and Technology of China · CNAnhui Provincial Children's Hospital · CNCase Western Reserve University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The NLRP1 inflammasome functions as canonical cytosolic sensor in response to intracellular infections and is implicated in auto-inflammatory diseases. But the regulation and signal transduction mechanisms of NLRP1 are incompletely understood. Here, we show that the T60 variant of CARD8, but not the canonical T48 isoform, negatively regulates the NLRP1 inflammasome activation by directly interacting with the receptor molecule NLRP1 and inhibiting inflammasome assembly. Furthermore, our results suggest that different ASC preference in three types of inflammasomes, namely the ASC-indispensable NLRP1 inflammasome, ASC-dispensable mNLRP1b inflammasome and ASC-independent CARD8 inflammasome, is mainly caused by the CARD domain, not the UPA subdomain. Based on the systematic site-directed mutagenesis and structural analysis, we find that signal transduction of the NLRP1 inflammasome relies on multiple interaction surfaces at its CARD domain. Finally, our results partly explain how mutations in NLRP1 lead to its constitutive activation in auto-inflammatory diseases. In conclusion, our study not only reveals how CARD8 downregulates the NLRP1 inflammasome activation, but also provides insights into the assembly mechanisms of CARD-containing inflammasomes.

Indexed as

InflammasomesNLR ProteinsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsSignal TransductionAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsInflammasomesNLR Proteinsautoinflammatory diseasesCARDCARD8death domain superfamilyNLRP1 inflammasome

Identifiers

PMID36426349
PMCPMC9679424
OpenAlexW4308424093

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.