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

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 V? and V? subfamilies. We identified 15 TCR? and 4 TCR? antigen receptor sequences shared between psoriasis patients and not observed in healthy controls or other inflammatory skin conditions. To address the relative roles of ?? versus ?? T cells in psoriasis, we carried out TCR/? HTS. These studies demonstrated that the majority of T cells in psoriasis and healthy skin are ?? T cells. ?? 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 ?? T cells. In summary, IL-17-producing ?? 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.

SUBMITTER: Matos TR 

PROVIDER: S-EPMC5663366 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature