Evidence map›Paper›PMID 28593945›Full record

ArticleNature communications2017

Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes.

Amit Lahiri, Matija Hedl, Jie Yan, Clara Abraham

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 9% 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

50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2023
    Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Tissue-specific transcriptional epistasis between Prkn and Lrrk2 during mycobacterial infection.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Article
  7. Response to Letter to the Editor.Human genomics · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Autophagy and Bacterial infections.Autophagy reports · 2025
    Review
  15. The research progress of LACC1.Frontiers in immunology · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
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

4 authors at 1 institution in 1 country.

Amit LahiriDepartment of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut 06510, USA.
Matija HedlDepartment of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut 06510, USA.
Jie YanDepartment of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut 06510, USA.
Clara AbrahamDepartment of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut 06510, USA.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1M
Yale University Inflammatory Bowel Disease Genetics Research CenterU01DK062422 · NIDDK · YALE UNIVERSITY · PI Ling-shiang Chuang · 2002 to 2026
$10.8M
Functional outcomes of inflammatory bowel disease associated variantsR01DK099097 · NIDDK · YALE UNIVERSITY · PI CLARA ABRAHAM · 2013 to 2026
$7.0M
NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK099097NIDDK NIH HHS U01 DK062422
6 · The paper itself

Abstract

Functional consequences for most inflammatory disease-associated loci are incompletely defined, including in the LACC1 (C13orf31) region. Here we show that human peripheral and intestinal myeloid-derived cells express laccase domain-containing 1 (LACC1); LACC1 is expressed in both the cytoplasm and mitochondria. Upon NOD2 stimulation of human macrophages, LACC1 associates with the NOD2-signalling complex, and is critical for optimal NOD2-induced signalling, mitochondrial ROS (mtROS) production, cytokine secretion and bacterial clearance. LACC1 constitutively associates with succinate dehydrogenase (SDH) subunit A, and amplifies pattern recognition receptor (PRR)-induced SDH activity, an important contributor to mtROS production. Relative to LACC1 Ile254, cells transfected with Crohn's disease-risk LACC1 Val254 or LACC1 with mutations of the nearby histidines (249,250) have reduced PRR-induced outcomes. Relative to LACC1 Ile254 carriers, Val254 disease-risk carrier macrophages demonstrate decreased PRR-induced mtROS, signalling, cytokine secretion and bacterial clearance. Therefore, LACC1 is critical for amplifying PRR-induced outcomes, an effect that is attenuated by the LACC1 disease-risk variant.

Indexed as

BacteriaCells, CulturedCrohn DiseaseCytokinesElectron Transport Complex IIExtracellular Signal-Regulated MAP KinasesHumansImmunity, InnateIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMacrophagesNF-kappa BNod2 Signaling Adaptor Proteinp38 Mitogen-Activated Protein KinasesProteinsReactive Oxygen SpeciesCytokinesElectron Transport Complex IIExtracellular Signal-Regulated MAP KinasesIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesLACC1 protein, humanNF-kappa BNOD2 protein, humanNod2 Signaling Adaptor Proteinp38 Mitogen-Activated Protein KinasesProteinsReactive Oxygen SpeciesReceptors, Pattern RecognitionRNA, Small InterferingSDHA protein, humanSuccinate Dehydrogenase

Identifiers

PMID28593945
PMCPMC5472760
OpenAlexW2624560002

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.