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- Title
Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones.
- Authors
Matos, Tiago R.; O'Malley, John T.; Lowry, Elizabeth L.; Hamm, David; Kirsch, Ilan R.; Robins, Harlan S.; Kupper, Thomas S.; Krueger, James G.; Clark, Rachael A.
- 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.
- Subjects
PSORIASIS; SKIN diseases; T cell receptors; IMMUNOSTAINING; ANTIGEN receptors; LYMPHOCYTES; PSORIASIS treatment; NONSTEROIDAL anti-inflammatory agents; AMINO acids; CELL culture; CELL receptors; INTERLEUKINS; NUCLEOTIDES; SKIN; CASE-control method; PHYSIOLOGY
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 11, p4031
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI93396