Evidence map›Paper›PMID 40680750›Full record

ArticleImmunity2025

Epigenetic silencing of interleukin-10 by host-derived oxidized phospholipids supports a lethal inflammatory response to infections.

Marco Di Gioia, Valentina Poli, Piao J Tan, Roberto Spreafico, Anne Chu, Alex G Cuenca, Zhongyang Wu, Mehdi Benamar, Laura Pandolfi, Federica Meloni and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Structural and molecular principles of DAMP biology.Nature structural & molecular biology · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. 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

21 authors.

Marco Di GioiaHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Valentina PoliHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Piao J TanDepartment of Chemical and Paper Engineering, Western Michigan University, Kalamazoo, MI, USA.
Roberto SpreaficoInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
Anne ChuHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Alex G CuencaDepartment of Surgery, Boston Children's Hospital, Boston, MA, USA; Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Zhongyang WuHarvard Medical School and Boston Children's Hospital, Division of Gastroenterology, Hepatology and Nutrition, Boston, MA, USA.
Mehdi BenamarHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Laura PandolfiRespiratory Disease Unit IRCCS San Matteo Hospital Foundation, and Department of Internal Medicine and Pharmacology, University of Pavia, Pavia, Italy.
Federica MeloniRespiratory Disease Unit IRCCS San Matteo Hospital Foundation, and Department of Internal Medicine and Pharmacology, University of Pavia, Pavia, Italy.
Fatemeh AskarianDepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Jason HsiaoDivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA.
Elizaveata BorroumDivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA.
Victor NizetDepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
Philip L S M GordtsDivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA; Department of Pathology, Division of Microbiology and Immunology, Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA.
Joseph L WitztumDivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Talal A ChatilaHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Janet ChouHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Xu ZhouHarvard Medical School and Boston Children's Hospital, Division of Gastroenterology, Hepatology and Nutrition, Boston, MA, USA.
James R SpringsteadDepartment of Chemical and Paper Engineering, Western Michigan University, Kalamazoo, MI, USA.
Ivan ZanoniHarvard Medical School and Boston Children's Hospital, Division of Immunology, Boston, MA, USA; Harvard Medical School and Boston Children's Hospital, Division of Gastroenterology, Hepatology and Nutrition, Boston, MA, USA. Electronic address: ivan.zanoni@childrens.harvard.edu.

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Tissue-specific roles of FXR in CVD and NASHP01HL147835 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2020 to 2024
$12.2M
Macrophage immunometabolism controls septic shockR01AI170632 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Ivan Zanoni · 2023 to 2026
$2.5M
Understanding Immune-Stromal Interactions in Tissue Homeostasis and InflammationR35GM151000 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI XU ZHOU · 2023 to 2026
$1.8M
NCATS NIH HHS UL1 TR001442NHLBI NIH HHS P01 HL147835NIAID NIH HHS R01 AI170632NIGMS NIH HHS R35 GM151000
6 · The paper itself

Abstract

Phagocytes initiate immunity to invading microorganisms by detecting pathogen-associated molecular patterns via pattern recognition receptors. Pathogen encounter and consequent activation of the immune system cause tissue damage and the release of host-derived damage-associated molecular patterns, contributing to shape immunity. However, how self-derived factors are sensed by phagocytes and impact the immune response remains poorly understood. Here, we demonstrated that host-derived oxidized phospholipids (oxPLs) are formed after microbial encounter in both mice and humans. oxPLs exacerbated inflammation without affecting pathogen burden. Mechanistically, oxPLs bound and inhibited AKT, potentiating the methionine cycle and the activity of the epigenetic writer EZH2. EZH2 epigenetically dampened the pluripotent anti-inflammatory cytokine IL-10, contributing to the death of the host. Overall, we found that host-derived oxPLs set the balance between protective and detrimental antimicrobial responses and that they can be prophylactically or therapeutically targeted to protect the host against deranged inflammation and immunopathology.

Indexed as

Epigenesis, GeneticInflammationInterleukin-10PhospholipidsAnimalsGene SilencingHumansMiceMice, Inbred C57BLOxidation-ReductionInterleukin-10PhospholipidsARDSdamage-associated molecular patternDAMPepigeneticmacrophagesPAMPpathogen-associated molecular patternpattern recognition receptorPRRsepsis

Identifiers

PMID40680750
PMCPMC12313134

What OpenQuestion holds

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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 OpenQuestion graph.