Evidence map›Paper›PMID 40316204›Full record

ArticleThe Journal of investigative dermatology2025

Unrestrained MyD88 Signaling in A20-Deficient Keratinocytes Triggers T-Cell-Dependent Psoriatic Arthritis-Like Disease.

Ryan Tobias, Sugandh Kumar, Jared Liu, Nika Lenci, Ameneh Gharabi, Dorothea Stibor, Rommel Advincula, Philip Achacoso, Zhi-Ming Huang, Christopher Bowman and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of investigative dermatology, 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

16 authors.

Ryan TobiasDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Sugandh KumarDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Jared LiuDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Nika LenciDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.
Ameneh GharabiDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Dorothea StiborDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.
Rommel AdvinculaDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.
Philip AchacosoDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.
Zhi-Ming HuangDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Christopher BowmanDepartment of Pathology, University of California San Francisco, San Francisco, California, USA.
Roberto Ricardo-GonzalezDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Mary C NakamuraDepartment of Medicine, University of California San Francisco, San Francisco, California, USA; San Francisco VA Health Care System, San Francisco, California, USA.
Wilson LiaoDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA.
Barbara A MalynnDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.
Averil MaDepartment of Medicine, University of California San Francisco, San Francisco, California, USA. Electronic address: Averil.Ma@ucsf.edu.
Bahram RazaniDepartment of Dermatology, University of California San Francisco, San Francisco, California, USA; San Francisco VA Health Care System, San Francisco, California, USA. Electronic address: Bahram.Razani@ucsf.edu.

Funding

RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
ELLIPSS: ELucidating the Landscape of Immunoendotypes in Psoriatic Skin and SynoviumUC2AR081029 · NIAMS · UNIVERSITY OF ROCHESTER · PI Johann Eli Gudjonsson, Wilson Liao · 2022 to 2026
$7.9M
Ubiquitination, Intestinal Homeostasis and CancerR01CA266755 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MA, AVERIL I · 2022 to 2025
$2.2M
Regulation of Ubiquitination and ArthritisR01AI135198 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MA, AVERIL I · 2018 to 2022
$2.0M
Ubiquitin and PsoriasisR01AI117908 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MA, AVERIL I · 2015 to 2019
$2.0M
Restriction of psoriatic skin and joint disease by A20K08AR077065 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RAZANI, BAHRAM · 2021 to 2025
$907k
Role of antiviral signaling in psoriatic pathogenesisR03AR082350 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RAZANI, BAHRAM · 2023 to 2023
$162k
NCI NIH HHS R01 CA266755NIAID NIH HHS R01 AI117908NIAID NIH HHS R01 AI135198NIAMS NIH HHS K08 AR077065NIAMS NIH HHS P30 AR070155NIAMS NIH HHS R03 AR082350NIAMS NIH HHS UC2 AR081029
6 · The paper itself

Abstract

Polymorphisms in A20 (TNFAIP3), a negative regulator of ubiquitin-mediated immune signaling, are strongly associated with psoriasis and psoriasis arthritis (PsA). The tissue-specific roles of A20 in preventing these diseases are poorly understood. Because cutaneous psoriasis typically precedes PsA by several years, skin inflammation may represent a key driver of joint disease. We now find that keratinocyte-specific deletion of A20 in normally developed adult mice spontaneously triggers both psoriasiform skin and joint disease, demonstrating a crucial role for epidermal A20 in restricting PsA-like pathology. Mice with A20-deficient keratinocytes that lack T cells were protected from PsA-like disease, showing a key role for epidermally triggered lymphocytes in driving joint inflammation. Early gene expression analysis after keratinocyte A20 deletion identified activation of MyD88 and antiviral signaling, reflecting spatial transcriptomic changes of human psoriatic epidermis. Keratinocyte-specific loss of A20 together with MyD88 but not germline disruption of IFN receptors in vivo protected mice from skin and joint pathology. A20-deficient primary keratinocytes from both mice and CRISPR-edited human cells spontaneously produced inflammatory cytokines and chemokines in vitro in a MyD88-dependent manner. A20-deficient murine keratinocytes also directly triggered IL-17A secretion from wild-type T cells. Together, our data demonstrate that keratinocyte A20 is critical for preventing T-cell-dependent PsA-like disease.

Indexed as

Arthritis, PsoriaticKeratinocytesMyeloid Differentiation Factor 88T-LymphocytesTumor Necrosis Factor alpha-Induced Protein 3AnimalsCells, CulturedDisease Models, AnimalHumansMiceMice, Inbred C57BLMice, KnockoutPsoriasisSignal TransductionMyd88 protein, mouseMyeloid Differentiation Factor 88Tnfaip3 protein, mouseTumor Necrosis Factor alpha-Induced Protein 3InflammationInnate ImmunologyNF-kBPsoriasisPsoriatic Arthritis

Identifiers

PMID40316204
PMCPMC13618700

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.