Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ.
Eur J Immunol
; 51(4): 915-929, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33296081
ABSTRACT
T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+ TOX+ EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+ TOX+ BHLHE40+ population of CD4+ , and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artrite Juvenil
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Proteínas de Grupo de Alta Mobilidade
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Linfócitos T
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Proteínas de Homeodomínio
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Proteínas com Domínio T
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Receptor de Morte Celular Programada 1
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Antígenos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha