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KMID : 0620920120440110694
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Experimental & Molecular Medicine
2012 Volume.44 No. 11 p.694 ~ p.705
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IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice
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Park Min-Jung
Park Hyun-Sil
Oh Hye-Joa
Lim Jung-Yeon
Yoon Bo-Young
Kim Ho-Youn
Cho Mi-La
Cho Seok-Goo
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Abstract
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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-α, IL-1β, 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.
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KEYWORD
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arthritis, experimental, bone marrow transplantation, interleukin-17, Th17 cells, T-lymphocytes, regulatory, transplantation, homologous
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