Cross-regulation of TNF and IFN-alpha in autoimmune diseases.
Proc Natl Acad Sci U S A
; 102(9): 3372-7, 2005 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-15728381
ABSTRACT
Cytokines, most particularly TNF and type I IFN (IFN-alphabeta), have been long considered essential elements in the development of autoimmunity. Identification of TNF in the pathogenesis of rheumatoid arthritis and TNF antagonist therapy represent successes of immunology. IFN-alphabeta plays a major role in systemic lupus erythematosus (SLE), a prototype autoimmune disease characterized by a break of tolerance to nuclear components. Here, we show that TNF regulates IFN-alpha production in vitro at two levels. First, it inhibits the generation of plasmacytoid dendritic cells (pDCs), a major producer of IFN-alphabeta, from CD34+ hematopoietic progenitors. Second, it inhibits IFN-alpha release by immature pDCs exposed to influenza virus. Neutralization of endogenous TNF sustains IFN-alpha secretion by pDCs. These findings are clinically relevant, as five of five patients with systemic juvenile arthritis treated with TNF antagonists display overexpression of IFN-alpha-regulated genes in their blood leukocytes. These results, therefore, might provide a mechanistic explanation for the development of anti-dsDNA antibodies and lupus-like syndrome in patients undergoing anti-TNF therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Factor de Necrosis Tumoral alfa
/
Interferón-alfa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos