OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response.
Immunity
; 42(6): 1159-70, 2015 Jun 16.
Article
em En
| MEDLINE
| ID: mdl-26070486
ABSTRACT
Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Auxiliares-Indutores
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Células Mieloides
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Ligante OX40
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Receptores OX40
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article