IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells.
EMBO J
; 36(1): 102-115, 2017 01 04.
Article
em En
| MEDLINE
| ID: mdl-27827809
ABSTRACT
Interleukin-1 (IL-1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL-1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL-1 receptor type 1 (IL-1R1)-dependent IL-1ß expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1ß did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM-CSF+ Th17 cell subset, thereby enhancing its encephalitogenic potential. Lack of expansion of GM-CSF-producing Th17 cells led to ameliorated disease in mice deficient for IL-1R1 specifically in T cells. Importantly, pathogenicity of IL-1R1-deficient T cells was fully restored by IL-23 polarization and expansion in vitro Therefore, our data demonstrate that IL-1 functions as a mitogenic mediator of encephalitogenic Th17 cells rather than qualitative inducer of their generation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Granulócitos e Macrófagos
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Interleucina-1
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Proliferação de Células
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Encefalomielite Autoimune Experimental
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Células Th17
Tipo de estudo:
Prognostic_studies
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Qualitative_research
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article