Evidence map›Paper›PMID 40769980›Full record

ArticleNature communications2025

IgG autoantibodies in bullous pemphigoid induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes.

Lei Bao, Christian F Guerrero-Juarez, Jing Li, Manuela Pigors, Shirin Emtenani, Yingzi Liu, Adrian P Mansini, Yulu F Wang, Aadil Ahmed, Norito Ishii and 15 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. Article
  2. Interleukin-24 in type 2 immune diseases.Frontiers in immunology · 2026
    Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Lei Bao *Department of Dermatology, Rush University Medical Center, Chicago, IL, USA.
Christian F Guerrero-Juarez *Department of Dermatology, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-6245-6412
Jing LiDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0009-0007-4228-0003
Manuela PigorsLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-3226-3935
Shirin EmtenaniLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Yingzi LiuDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-8704-4756
Adrian P MansiniDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA.
Yulu F WangDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA.
Aadil AhmedDepartment of Pathology, Rush University Medical Center, Chicago, IL, USA.
Norito IshiiDepartment of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
Takashi HashimotoDepartment of Dermatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Bethany E Perez WhiteDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-5594-0599
Stefan GreenGenomics and Microbiome Core Facility, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-2781-359X
Kevin KunstmanGenomics and Microbiome Core Facility, Rush University Medical Center, Chicago, IL, USA.
Nicole C NowakDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA.
Connor ColeDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA.
Mrinal K SarkarDepartments of Internal Medicine and Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-8505-4259
Johann E GudjonssonDepartments of Internal Medicine and Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-0080-0812
Macias VirgiliaDepartment of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
Maria SverdlovResearch Histology Core, Research Resources Center, University of Illinois at Chicago, Chicago, IL, USA.
M Allen McAlexanderTranslational Science and Experimental Medicine, Early Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, USA.
Christopher McCraeTranslational Science and Experimental Medicine, Early Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, USA.
Christopher D NazaroffTranslational Science and Experimental Medicine, Early Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0002-5063-8788
Enno SchmidtLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-1206-8913
Kyle T AmberDepartment of Dermatology, Rush University Medical Center, Chicago, IL, USA. kyle_amber@rush.edu.ORCID http://orcid.org/0000-0002-2906-2454

Funding

University of Michigan Skin Biology and Diseases Resource-based CenterP30AR075043 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$649k
AstraZeneca 10046533NIAMS NIH HHS P30 AR075043NIH HHS R21 OD030057U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) P30AR075043
6 · The paper itself

Abstract

Autoantibodies in bullous pemphigoid (BP) are known to activate the innate immune response. Nevertheless, the direct effect of autoantibodies on keratinocytes and the contribution of keratinocyte responses to the pathology of BP are largely unknown. Here, by performing multiplex immunoassays and RNA-seq on primary keratinocytes treated with IgG derived from BP patients, we identify a MyD88-dependent pro-inflammatory and proteolytic response characterized by the release of several cytokines (IL-6, IL-24, TGF-β1), chemokines (CXCL16, MIP-3β, RANTES), C1s, DPP4, and MMP-9. The activation of this MyD88-dependent response is further validated using spatial transcriptomics and scRNA-seq of diseased skin. Blistering of the skin appears to significantly impact this inflammatory response, with attached BP skin and spongiotic dermatitis revealing indistinguishable transcriptomes. In a preclinical mouse model of BP, Krt14-specific Myd88 knockout significantly decreases disease severity and reduces serum levels of IL-4 and IL-9, indicating a contributory role of keratinocyte-derived skin inflammation in the systemic response. Thus, our work highlights key contributions of keratinocytes in response to autoantibodies in BP.

Indexed as

AutoantibodiesImmunoglobulin GKeratinocytesMyeloid Differentiation Factor 88Pemphigoid, BullousAnimalsCytokinesDisease Models, AnimalFemaleHumansInflammationMaleMiceMice, Inbred C57BLMice, KnockoutSkinAutoantibodiesCytokinesImmunoglobulin GMYD88 protein, humanMyd88 protein, mouseMyeloid Differentiation Factor 88

Identifiers

PMID40769980
PMCPMC12329039

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.