An essential protective role of IL-10 in the immunological mechanism underlying resistance vs. susceptibility to lupus induction by dendritic cells and dying cells.
Rheumatology (Oxford)
; 50(10): 1773-84, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21727182
ABSTRACT
OBJECTIVE:
To define the role of IL-10 in lupus pathogenesis, and to understand the immunological mechanisms underlying resistance vs susceptibility to lupus disease induction by dendritic cells (DCs) and dying cells.METHODS:
Groups of IL-10-deficient and normal C57BL/6 mice were injected with syngenic DCs that had ingested necrotic cells prepared by either freeze-thaw cycle (DC/nec(F/T)) or heat shock (DC/nec(H/S)) procedures, or with DC or necrotic cells alone, or with PBS only. Disease development, including proteinuria and renal pathological changes, was monitored. Levels of autoantibodies against different lupus-associated nuclear antigens were measured by ELISAs, and IC deposition in the kidneys was confirmed by immunostaining.RESULTS:
No significant proteinuria was detected in the mice. However, striking renal pathological changes typical of IC-mediated GN were consistently observed in the DC/nec(F/T)-treated IL-10(-/-) mice. These included glomerular hypercellularity and macrophage infiltration, renal IC deposition, circulating kidney-reactive autoantibodies and the presence of immunoglobulin G2 isotype-specific antibody complexes in the diseased kidneys. We demonstrated further that host-derived IL-10 was primarily responsible for protecting against the induction of pathogenic Th1 type of autoantibody responses in the mice.CONCLUSION:
IL-10 protects against the induction of lupus-like renal end-organ damage by down-regulating pathogenic Th1 responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Interleucina-10
/
Imunidade Inata
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article