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 ...
    • Next-Generation Sequencing in Medicine (Upcoming)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • 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
  • Concise Communication
  • 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 4

Putative pathogenic T cell clones are also present in lower numbers in the nonlesional skin from psoriasis patients.

Options: View larger image (or click on image) Download as PowerPoint
Putative pathogenic T cell clones are also present in lower numbers in t...
(A) Expanded oligoclonal populations of T cells are present in nonlesional skin. The total T cells per unit skin (100 ng of skin DNA) of the top 20 most frequent T cell clones are shown for nonlesional skin from 7 psoriatic patients (nonlesional psoriasis [NL], far right). Three skin samples from healthy individuals (healthy controls [HC]) and 4 clinically resolved psoriatic lesions (resolved psoriasis, healed lesion [HL]) are included for comparison. (B) Putative pathogenic T cells are detected in the nonlesional skin of patients with psoriasis. Putative pathogenic clones were defined as the most frequent T cell clones in resolved lesions that were also present in active lesions. Clone-tracking analyses were used to measure the frequency of the top 5 most frequent of these T cell clones in active lesions (Lesion), resolved lesions (Resolved), and nonlesional skin from the same patient (Non-les). The frequency of these T cell clones was highest in resolved lesions, followed by active lesions, and was lowest in the nonlesional skin. Data from 5 patients are shown; 5 additional patients showed a similar pattern. (C) In addition to being more frequent, putative pathogenic clones were present in highest absolute numbers in resolved lesions. The absolute number of T cells per 100 ng of total DNA is shown for the most frequent putative pathogenic T cell clone in 7 patients. (D) Overlap analyses demonstrate that shared T cell clones among lesional, resolved, and nonlesional skin (red circles) are among the most frequent T cell clones in both active and resolved psoriatic lesions. Two representative analyses out of a total of 7 are shown.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts