Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αß T cell clones.
J Clin Invest
; 127(11): 4031-4041, 2017 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-28945199
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 Vß and Vα subfamilies. We identified 15 TCRß 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 αß 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 αß 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 αß T cells. In summary, IL-17-producing αß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Células Th17
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos