Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity.
Immunity
; 19(3): 437-50, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-14499118
ABSTRACT
Suppressor of cytokine signaling-1 (SOCS1/JAB) negatively regulates not only the cytokine-signaling pathway but also lipopolysaccharide (LPS)-induced macrophage activation. We found that SOCS1-deficient dendritic cells (DCs) were also hyperresponsive to interferon-gamma and interleukin-4. To define the role of SOCS1-deficient DCs in vivo, we generated mice in which the SOCS1 expression was restored in T and B cells on a SOCS1(-/-) background. In these mice, DCs were accumulated in the thymus and spleen and produced high levels of BAFF/BLyS and APRIL, resulting in the aberrant expansion of B cells and autoreactive antibody production. SOCS1-deficient DCs efficiently stimulated B cell proliferation in vitro and autoantibody production in vivo. These results indicate that SOCS1 plays an essential role in the normal DC functions and suppression of systemic autoimmunity.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Células Dendríticas
/
Proteínas de Transporte
/
Autoimunidade
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article