Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
An IGFBP7hi endothelial cell subset drives T cell extravasation in psoriasis via endothelial glycocalyx degradation
Qingyang Li, … , Erle Dang, Gang Wang
Qingyang Li, … , Erle Dang, Gang Wang
Published March 14, 2023
Citation Information: J Clin Invest. 2023;133(9):e160451. https://doi.org/10.1172/JCI160451.
View: Text | PDF
Research Article Inflammation Vascular biology Article has an altmetric score of 1

An IGFBP7hi endothelial cell subset drives T cell extravasation in psoriasis via endothelial glycocalyx degradation

  • Text
  • PDF
Abstract

Dysfunction of vascular endothelial cells (ECs) facilitates imbalanced immune responses and tissue hyperinflammation. However, the heterogeneous functions of skin ECs and their underlying mechanism in dermatoses remain to be determined. Here, focusing on the pathogenic role of skin ECs in psoriasis, we characterized the molecular and functional heterogeneity of skin ECs from healthy individuals and psoriasis patients at the single-cell level. We found that endothelial glycocalyx destruction, a major feature of EC dysfunction in psoriasis, was a driving force during the process of T cell extravasation. Interestingly, we identified a skin EC subset, IGFBP7hi ECs, in psoriasis. This subset actively responded to psoriatic-related cytokine signaling, secreted IGFBP7, damaged the endothelial glycocalyx, exposed the adhesion molecules underneath, and prepared the endothelium for immune-cell adhesion and transmigration, thus aggravating skin inflammation. More importantly, we provided evidence in a psoriasis-like mouse model that anti-IGFBP7 treatment showed promising therapeutic effects for restoring the endothelial glycocalyx and alleviating skin inflammation. Taken together, our results depict the distinct functions of EC clusters in healthy and psoriatic skin, identify IGFBP7hi ECs as an active subset modulating vascular function and cutaneous inflammation, and indicate that targeting IGFBP7 is a potential therapeutic strategy in psoriasis.

Authors

Qingyang Li, Shuai Shao, Zhenlai Zhu, Jiaoling Chen, Junfeng Hao, Yaxing Bai, Bing Li, Erle Dang, Gang Wang

×

Figure 5

IGFBP7hi ECs accumulate in papillary vessels of psoriasis skin.

Options: View larger image (or click on image) Download as PowerPoint
IGFBP7hi ECs accumulate in papillary vessels of psoriasis skin.
(A) Immu...
(A) Immunofluorescence staining of IGFBP7, CD31, and Hoechst in skin tissues from healthy individuals and psoriasis patients (n = 7 skin samples/group). The yellow dashed lines mark the interface between the epidermis and dermis. The green dashed lines indicate the outline of ECs. The yellow arrowheads indicate skin ECs that express IGFBP7. Schematic of papillary and subpapillary vessels in the psoriatic skin lesion is shown on the right. (B) The percentages of IGFBP7hi ECs in blood vessels of healthy and psoriatic skin in A were quantified (n = 21 views of 7 skin samples/group). (C) Immunofluorescence staining for IGFBP7, CD31, and Hoechst in IMQ-induced psoriatic skin lesions and perilesions (n = 6 mice). The yellow dashed lines mark the interface between the epidermis and dermis. The green dashed lines indicate the outline of ECs. (D) Percentages of IGFBP7hi ECs in blood vessels were quantified (n = 18 views of 6 skin samples/group). (E) IGFBP7 levels in peripheral blood from patients (n = 20 blood samples/group). (F) Linear regression analysis of the correlation between serum IGFBP7 and the psoriasis area and severity index (PASI) in psoriasis patients. Data are represented as mean ± SD. Analysis of data in B was performed using 1-way ANOVA with Tukey’s post hoc test. Data in D and E were analyzed using unpaired Student’s t test.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 2 X users
14 readers on Mendeley
See more details