High-throughput T cell receptor sequencing identifies clonally expanded CD8+ T cell populations in alopecia areata.
JCI Insight
; 3(19)2018 10 04.
Article
em En
| MEDLINE
| ID: mdl-30282836
ABSTRACT
Alopecia areata (AA) is an autoimmune disease in which cytotoxic T cells specifically target growing hair follicles. We used high-throughput TCR sequencing in the C3H/HeJ mouse model of AA and in human AA patients to gain insight into pathogenic T cell populations and their dynamics, which revealed clonal CD8+ T cell expansions in lesional skin. In the C3H/HeJ model, we observed interindividual sharing of TCRß chain protein sequences, which strongly supports a model of antigenic drive in AA. The overlap between the lesional TCR repertoire and a population of CD8+NKG2D+ T cells in skin-draining lymph nodes identified this subset as pathogenic effectors. In AA patients, treatment with the oral JAK inhibitor tofacitinib resulted in a decrease in clonally expanded CD8+ T cells in the scalp but also revealed that many expanded lesional T cell clones do not completely disappear from either skin or blood during treatment with tofacitinib, which may explain in part the relapse of disease after stopping treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Receptores de Antígenos de Linfócitos T
/
Linfócitos T CD8-Positivos
/
Alopecia em Áreas
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2018
Tipo de documento:
Article