IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice

• Published in: Experimental & molecular medicine Vol. 44; no. 11; pp. 694 - 705
• Main Authors: Park, Min-Jung, Park, Hyun-Sil, Oh, Hye-Joa, Lim, Jung-Yeon, Yoon, Bo-Young, Kim, Ho-Youn, Cho, Mi-La, Cho, Seok-Goo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2012; Springer Nature B.V; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Animals; Antigens, Differentiation - metabolism; Arthritis, Experimental - pathology; Arthritis, Experimental - prevention & control; Biomedical and Life Sciences; Biomedicine; Bone Marrow Transplantation; Cell Differentiation; Cell Proliferation; Cells, Cultured; Collagen Type II; Cytokines - metabolism; Humans; Interleukin-17 - deficiency; Interleukin-17 - genetics; Joints - pathology; Male; Medical Biochemistry; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Molecular Medicine; Original; Osteoclasts - metabolism; Osteoclasts - physiology; Signal Transduction; Stem Cells; T-Lymphocytes - metabolism; T-Lymphocytes - physiology; Transplantation, Homologous; 생화학; T-lymphocytes, regulatory; interleukin-17; arthritis, experimental; bone marrow transplantation; Th17 cells; transplantation, homologous
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2012.44.11.078

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.