IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice
Experimental & Molecular Medicine
; : 694-705, 2012.
Article
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| ID: wpr-149759
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WPRO
ABSTRACT
IL-17-producing CD4+ T cells (Th17) play important functions in autoimmune diseases and allograft rejection of solid organs. We examined the effects of IL 17 and its mechanism of action on arthritis in a murine collagen-induced arthritis (CIA) model using bone marrow transplantation (BMT) system. DBA/1J mice were administered a lethal radiation dose and then rescued with bone marrow derived from either wild-type (WT) or IL-17-/- mice on C57BL/6 background mice. CIA was induced after the bone marrow transplant, and disease progression was characterized. DBA/1J mice with CIA that received IL-17-/- donor bone marrow showed potently inhibited development and severity of clinical arthritis as compared with CIA mice that received WT bone marrow. Reduced secretion of the pro-inflammatory cytokines tumor necrosis factor-alpha, IL-1beta, and IL-6, and collagen-specific T cell responses were observed in mice that received IL-17-/- bone marrow. IL-17 blockade also inhibited effector T cell proliferation by reciprocally regulating the Treg/Th17 ratio. IL-17 blockade prevented joint destruction in mice with CIA. These findings suggest that CIA with BMT is a viable method of immunological manipulation and that IL-17 deficiency suppresses severe joint destruction and inflammation in CIA mice. There may be clinical benefits in blocking IL-17 and BMT in the treatment of rheumatoid arthritis.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Ostéoclastes
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Arthrite expérimentale
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Transplantation homologue
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Lymphocytes T
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Transduction du signal
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Antigènes de différenciation
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Différenciation cellulaire
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Cellules cultivées
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Cytokines
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Transplantation de moelle osseuse
Type d'étude:
Prognostic_studies
Limites du sujet:
Animals
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Humans
/
Male
langue:
En
Texte intégral:
Experimental & Molecular Medicine
Année:
2012
Type:
Article