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

Authors
  • Matos, Tiago R1, 2, 3
  • O'Malley, John T1
  • Lowry, Elizabeth L1
  • Hamm, David4
  • Kirsch, Ilan R4
  • Robins, Harlan S4
  • Kupper, Thomas S1
  • Krueger, James G5
  • Clark, Rachael A1
  • 1 Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 2 Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. , (Portugal)
  • 3 Academic Medical Center, Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands. , (Netherlands)
  • 4 Adaptive Biotechnologies, Seattle, Washington, USA.
  • 5 Department of Dermatology, Rockefeller University, New York, New York, USA.
Type
Published Article
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Publication Date
Nov 01, 2017
Volume
127
Issue
11
Pages
4031–4041
Identifiers
DOI: 10.1172/JCI93396
PMID: 28945199
Source
Medline
License
Unknown

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.

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