Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • 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
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editor's notes
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Clinically resolved psoriatic lesions contain psoriasis-specific IL-17–producing αβ T cell clones
Tiago R. Matos, … , James G. Krueger, Rachael A. Clark
Tiago R. Matos, … , James G. Krueger, Rachael A. Clark
Published September 25, 2017
Citation Information: J Clin Invest. 2017;127(11):4031-4041. https://doi.org/10.1172/JCI93396.
View: Text | PDF
Research Article Dermatology

Clinically resolved psoriatic lesions contain psoriasis-specific IL-17–producing αβ T cell clones

  • Text
  • PDF
Abstract

In psoriasis, an IL-17–mediated inflammatory skin disease, skin lesions resolve with therapy, but often recur in the same locations when therapy is discontinued. We propose that residual T cell populations in resolved psoriatic lesions represent the pathogenic T cells of origin in this disease. Utilizing high-throughput screening (HTS) of the T cell receptor (TCR) and immunostaining, we found that clinically resolved psoriatic lesions contained oligoclonal populations of T cells that produced IL-17A in both resolved and active psoriatic lesions. Putative pathogenic clones preferentially utilized particular Vβ and Vα subfamilies. We identified 15 TCRβ and 4 TCRα antigen receptor sequences shared between psoriasis patients and not observed in healthy controls or other inflammatory skin conditions. To address the relative roles of αβ versus γδ T cells in psoriasis, we carried out TCR/δ HTS. These studies demonstrated that the majority of T cells in psoriasis and healthy skin are αβ T cells. γδ T cells made up 1% of T cells in active psoriasis, less than 1% in resolved psoriatic lesions, and less than 2% in healthy skin. All of the 70 most frequent putative pathogenic T cell clones were αβ T cells. In summary, IL-17–producing αβ T cell clones with psoriasis-specific antigen receptors exist in clinically resolved psoriatic skin lesions. These cells likely represent the disease-initiating pathogenic T cells in psoriasis, suggesting that lasting control of this disease will require suppression of these resident T cell populations.

Authors

Tiago R. Matos, John T. O’Malley, Elizabeth L. Lowry, David Hamm, Ilan R. Kirsch, Harlan S. Robins, Thomas S. Kupper, James G. Krueger, Rachael A. Clark

×

Figure 2

Residual T cell populations and expanded T cell clones in clinically resolved psoriatic lesions produce key pathogenic cytokines in psoriasis.

Options: View larger image (or click on image) Download as PowerPoint
Residual T cell populations and expanded T cell clones in clinically res...
(A) IL-17A and IL-22 are produced by residual T cell populations in clinically resolved psoriatic lesions. T cells were isolated from biopsies of clinically resolved psoriasis after UVB phototherapy, and their cytokine production was studied by intracellular cytokine staining and flow cytometry. The mean results of healthy skin (n = 4) and resolved psoriasis lesions (n = 3) are shown. (B–E) Expanded T cell clones identified by HTS produce IL-17A in healed lesions. HTS was used to identify the TCR Vβ subunit used by T cell clones expanded in resolved lesions. Three patients in the cohort had oligoclones in resolved lesions that used the VB03 or VB05 genes that correspond to the use of the TCR Vβ9 and Vβ5.1 protein subunits by T cells, respectively. Costaining for (B) Vβ5.1-expressing and (E) Vβ9-expressing T cells and IL-17A in these patients is shown. Individual values and the mean from 3 patients of the (C) percentage of Vβ+ T cells producing IL-17A and (D) the proportion of total IL-17A produced by Vβ+ T cells are shown.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts