Evidence map›Paper›PMID 33864770›Full record

ArticleThe Journal of investigative dermatology2021

IRAK2 Has a Critical Role in Promoting Feed-Forward Amplification of Epidermal Inflammatory Responses.

Shuai Shao, Lam C Tsoi, William R Swindell, Jiaoling Chen, Ranjitha Uppala, Allison C Billi, Xianying Xing, Chang Zeng, Mrinal K Sarkar, Rachael Wasikowski and 18 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of investigative dermatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

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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

28 authors at 8 institutions in 3 countries.

Shuai ShaoDepartment of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Lam C TsoiDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
William R SwindellDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Jiaoling ChenDepartment of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Ranjitha UppalaDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Allison C BilliDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Xianying XingDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Chang ZengDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Mrinal K SarkarDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Rachael WasikowskiDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Yanyun JiangDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Joseph KirmaDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Jingru SunDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Olesya PlazyoDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Gang WangDepartment of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Paul W HarmsDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
John J VoorheesDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Nicole L WardDepartments of Nutrition and Dermatology, School of Medicine, Case Western University, Cleveland, Ohio, USA.
Feiyang MaDepartment of UCLA Dermatology, UCLA Medical School, Los Angeles, California, USA.
Matteo PellegriniDepartment of UCLA Dermatology, UCLA Medical School, Los Angeles, California, USA.
Alexander MerleevDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA.
Bethany E Perez WhiteDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Robert L ModlinDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Bogi AndersenDepartment of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USA.
Emanual MaverakisDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA.
Stephan WeidingerDepartment of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
J Michelle KahlenbergDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Johann E GudjonssonDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: johanng@med.umich.edu.
University of Michigan · USUniversity of California, Davis · USXijing Hospital · CNCase Western Reserve University · USNorthwestern University · USUniversity Hospital Schleswig-Holstein · DEUniversity of California, Irvine · USUniversity of California, Los Angeles · US

Funding

TCR GAMMA/DELTA LYMPHOCYTES IN HUMAN SKIN LESIONSR01AR040312 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MODLIN, ROBERT L · 1990 to 2025
$10.4M
Microbiology and Metagenomics CoreP50AR080594 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROBERT L MODLIN · 2022 to 2026
$9.2M
Transcriptional Co-Regulators in EpidermisR01AR044882 · NIAMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI Bogi Andersen · 1998 to 2026
$9.0M
Northwestern University Skin Disease Research Center Resource-based CenterP30AR075049 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Irina Budunova · 2019 to 2026
$6.6M
University of Michigan Skin Biology and Diseases Resource-based CenterP30AR075043 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANDRZEJ A. DLUGOSZ · 2019 to 2026
$6.6M
Psoriasis Center of Research TranslationP50AR070590 · NIAMS · CASE WESTERN RESERVE UNIVERSITY · PI COOPER, KEVIN D, MCCORMICK, THOMAS S · 2017 to 2021
$6.5M
University of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1M
UCI P30 Skin Center Systems Biology CoreP30AR075047 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANDERSEN, BOGI, GANESAN, ANAND K · 2019 to 2025
$5.1M
Kallikrein-PAR interactions in skin inflammationR01AR073196 · NIAMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARD, NICOLE LEANNE · 2018 to 2023
$3.3M
Role of IL-13 and the IL-13 Associated rs20541 Risk Variant in the Pathogenesis of PsoriasisR01AR069071 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GUDJONSSON, JOHANN ELI · 2015 to 2019
$2.1M
Role of the Psoriasis Associated IL23R Risk Variants on Th17 Biology and FunctionK08AR060802 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GUDJONSSON, JOHANN ELI · 2011 to 2015
$636k
Integrative Biology Approach to Identify and Characterize Roles of lncRNAs Associated with Psoriasis PathologyK01AR072129 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TSOI, LAM CHEUNG · 2017 to 2021
$500k
NIAMS NIH HHS K01 AR072129NIAMS NIH HHS K01 AR072773NIAMS NIH HHS K08 AR060802NIAMS NIH HHS L40 AR076139NIAMS NIH HHS P30 AR075043NIAMS NIH HHS P30 AR075047NIAMS NIH HHS P30 AR075049NIAMS NIH HHS P50 AR070590NIAMS NIH HHS P50 AR080594NIAMS NIH HHS R01 AR040312NIAMS NIH HHS R01 AR044882NIAMS NIH HHS R01 AR069071NIAMS NIH HHS R01 AR073196NIGMS NIH HHS R25 GM086262
6 · The paper itself

Abstract

Many inflammatory skin diseases are characterized by altered epidermal differentiation. Whether this altered differentiation promotes inflammatory responses has been unknown. Here, we show that IRAK2, a member of the signaling complex downstream of IL-1 and IL-36, correlates positively with disease severity in both atopic dermatitis and psoriasis. Inhibition of epidermal IRAK2 normalizes differentiation and inflammation in two mouse models of psoriasis- and atopic dermatitis-like inflammation. Specifically, we demonstrate that IRAK2 ties together proinflammatory and differentiation-dependent responses and show that this function of IRAK2 is specific to keratinocytes and acts through the differentiation-associated transcription factor ZNF750. Taken together, our findings suggest that IRAK2 has a critical role in promoting feed-forward amplification of inflammatory responses in skin through modulation of differentiation pathways and inflammatory responses.

Indexed as

Cell DifferentiationCells, CulturedDermatitis, AtopicEpidermisHumansInflammationInterleukin-1 Receptor-Associated KinasesNF-kappa BPsoriasisSeverity of Illness IndexSignal TransductionTranscription FactorsTumor Suppressor ProteinsInterleukin-1 Receptor-Associated KinasesNF-kappa BTranscription FactorsTumor Suppressor ProteinsZNF750 protein, human

Identifiers

PMID33864770
PMCPMC9423738
OpenAlexW3156060652

What OpenQuestion holds

Textmetadata
LicenceTDM
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.