IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice.
- Author:
Min Jung PARK
1
;
Hyun Sil PARK
;
Hye Joa OH
;
Jung Yeon LIM
;
Bo Young YOON
;
Ho Youn KIM
;
Mi La CHO
;
Seok Goo CHO
Author Information
1. Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea. iammila@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
arthritis, experimental;
bone marrow transplantation;
interleukin-17;
Th17 cells;
T-lymphocytes, regulatory;
transplantation, homologous
- MeSH:
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
- From:Experimental & Molecular Medicine
2012;44(11):694-705
- CountryRepublic of Korea
- Language:English
-
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.
