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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.
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Research Article Dermatology

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

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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

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Figure 6

αβ T cells predominate in psoriatic and healthy human skin, and putative pathogenic clones in psoriasis were αβ T cells that utilized a skewed Vα repertoire and contained common TCRα CDR3 sequences not observed in healthy controls.

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αβ T cells predominate in psoriatic and healthy human skin, and putative...
(A–C) Sequencing of the TCRα/δ locus revealed that αβ T cells predominate in psoriatic lesions and healthy human skin and putative pathogenic T cells were universally α T cells. The percentages of αβ versus γδ T cells in (A) active psoriatic lesions (n = 10), (B) resolved psoriatic lesions (n = 10), and skin from healthy controls (n = 3), and among (C) putative pathogenic T cell clones in psoriasis are shown. Results are also summarized in Table 2. (D) Putative pathogenic T cell clones preferentially utilized Vα20, Vα30, and Vα41, as compared with 16,517 TCRα sequences from the skin of 6 healthy controls (χ2 test). (E and F) T cells with highly similar TCR Vα CDR3 sequences (1 or 2 nucleotides different, 4 pairs of patients) or clearly distinct Vα CDR3 sequences (1 patient pair) giving rise to identical CDR3 amino acid sequences were found in common between patients with psoriasis. These shared CDR3 amino acid sequences were not observed in healthy controls. Shared receptors are listed in Table 1.

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

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