Evidence map›Paper›PMID 41413388›Full record

ArticleNature communications2025

IL-17A is increased in diabetic wounds and impairs keratinocyte function via histone demethylase JMJD3.

Jadie Y Moon, Sonya J Wolf, Amrita D Joshi, He Zhang, James Shadiow, Tyler M Bauer, Kevin D Mangum, Lindsey D Hughes, Christopher O Audu, William J Melvin and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. 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
–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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

24 authors.

Jadie Y MoonGraduate Program in Immunology, University of Michigan, Ann Arbor, MI, USA.
Sonya J WolfDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA. sonwolf@med.umich.edu.ORCID http://orcid.org/0000-0003-3626-9274
Amrita D JoshiSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
He ZhangDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0009-0001-1899-2402
James ShadiowSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-0293-6753
Tyler M BauerSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-5430-5104
Kevin D MangumSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Lindsey D HughesSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-1764-4553
Christopher O AuduSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-4183-8825
William J MelvinSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3241-5919
Emily C BarrettSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Sabrina RoccoSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-7822-072X
Gabriela Saldana de JimenezSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Amber L EstorSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Moses NelapudiSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Qinmengge LiDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.
Rachael BogleDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-3544-3023
Benjamin LeviDepartment of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Frank M DavisSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Andrea T ObiSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Bethany B MooreDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
Lam C TsoiDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.
Johann E GudjonssonDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-0080-0812
Katherine A GallagherDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA. kgallag@med.umich.edu.ORCID http://orcid.org/0000-0002-8791-6980

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
RESEARCH TRAINING IN EXPERIMENTAL IMMUNOPATHOLOGYT32AI007413 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Bethany B. Moore · 1993 to 2026
$9.8M
Notch signaling in diabetic woundsR01DK127531 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN · 2021 to 2024
$2.5M
The Interferon-beta (IFN-beta)/SETDB2 Epigenetic Axis Regulates Inflammation And Metabolism In Diabetic WoundsR01HL137919 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN · 2017 to 2021
$2.4M
Epigenetic Regulation of Prostaglandin E2 (PGE2) Synthesis Alters Macrophage Function to Promote Inflammation and Impair Diabetic Wound HealingR01DK124290 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN, MOORE, BETHANY B. · 2020 to 2023
$1.8M
Epigenetic regulation of keratinocyte function in normal and pathologic skin repairF31DK136199 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOON, JADIE · 2023 to 2025
$118k
NHLBI NIH HHS R01 HL137919NIAID NIH HHS T32 AI007413NIDDK NIH HHS F31 DK136199NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK124290NIDDK NIH HHS R01 DK127531U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01-HL137919 (KAG)
6 · The paper itself

Abstract

IL-17A is a cytokine critical for tissue repair, but in excess, it prolongs inflammation and impairs healing. In type 2 diabetic (T2D) wounds, keratinocyte functions, including migration and inflammation, are disrupted, though mechanisms remain unclear. Here, we demonstrate that IL-17A regulates keratinocyte dysfunction via induction of the histone demethylase Jumonji domain-containing protein 3 (JMJD3) through a TRAF6/NFκB pathway. JMJD3 removes repressive histone 3 lysine 27 (H3K27me3) marks at anti-migratory (Itga3, Timp1) and inflammatory (Ccl20, Cxcl1, Cxcl3, Cxcl5) gene promoters, increasing transcription. Human and murine diabetic wounds exhibit elevated IL-17A signaling, JMJD3, and expression of associated anti-migratory and inflammatory genes compared to controls. Importantly, keratinocyte-specific deletion of IL-17A signaling or JMJD3 in diabetic mice improves wound healing and decreases expression of JMJD3 target genes. These findings reveal an IL-17A/JMJD3-mediated mechanism driving keratinocyte dysfunction in T2D wounds and highlight the therapeutic potential of targeting this axis to enhance wound repair.

Indexed as

Diabetes Mellitus, Type 2Interleukin-17Jumonji Domain-Containing Histone DemethylasesKeratinocytesAnimalsCell MovementDiabetes Mellitus, ExperimentalFemaleHumansInflammationMaleMiceMice, Inbred C57BLMice, KnockoutNF-kappa BSignal TransductionIL17A protein, humanIl17a protein, mouseInterleukin-17Jumonji Domain-Containing Histone DemethylasesKDM6B protein, humanKdm6b protein, mouseNF-kappa B

Identifiers

PMID41413388
PMCPMC12824406

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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.