title: IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice.
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-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.
authors.affiliation: Rheumatism Research Center, Catholic Research Institutes of Medical Science, Seoul, Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Hyun Sil
authors.initials: HS
authors.lastname: Park
authors.forename: Hye Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Lim
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Yoon
authors.forename: Ho Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Mi La
authors.initials: ML
authors.lastname: Cho
authors.forename: Seok Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000172:deficiency* / Q000235:genetics; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D000943:Antigens, Differentiation; D024043:Collagen Type II; D016207:Cytokines; D020381:Interleukin-17