Exp Mol Med.
2012 Nov;44(11):694-705.
IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice
- Affiliations
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- 1Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea. iammila@catholic.ac.kr
- 2Immune Tolerance Research Center, Convergent Research Consortium for Immunologic Disease (CRCID), The Catholic University of Korea College of Medicine, Seoul 137-701, Korea. chosg@catholic.ac.kr
- 3Catholic Blood and Marrow Transplantation Center, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea.
- 4Department of Internal Medicine, Inje University Ilsan Paik Hospital, Seoul 411-706, Korea.
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.
Keyword
MeSH Terms
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Animals
Antigens, Differentiation/metabolism
Arthritis, Experimental/pathology/*prevention & control
*Bone Marrow Transplantation
Cell Differentiation
Cell Proliferation
Cells, Cultured
Collagen Type II
Cytokines/metabolism
Humans
Interleukin-17/*deficiency/genetics
Joints/pathology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Osteoclasts/metabolism/physiology
Signal Transduction
T-Lymphocytes/metabolism/physiology
Transplantation, Homologous
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