title: Gut-residing Microbes Alter the Host Susceptibility to Autoantibody-mediated Arthritis.
abstract: K/BxN serum can transfer arthritis to normal mice owing to the abundant autoantibodies it contains, which trigger innate inflammatory cascades in joints. Little is known about whether gut-residing microbes affect host susceptibility to autoantibody-mediated arthritis. To address this, we fed C57BL/6 mice with water containing a mixture of antibiotics (ampicillin, vancomycin, neomycin, and metronidazol) for 2 weeks and then injected them with K/BxN serum. Antibiotic treatment significantly reduced the amount of bacterial genomic DNA isolated from fecal samples, in particular a gene encoding 16S ribosomal RNA derived from segmented filamentous bacteria. Arthritic signs, as indicated by the arthritic index and ankle thickness, were significantly attenuated in antibiotic-treated mice compared with untreated controls. Peyer's patches and mesenteric lymph nodes from antibiotic-treated mice contained fewer IL-17-expressing cells than those from untreated mice. Antibiotic treatment reduced serum C3 deposition in vitro via the alternative complement pathway. IL-17(-/-) congenic C57BL/6 mice were less susceptible to K/BxN serum-transferred arthritis than their wild-type littermates, but were still responsive to treatment with antibiotics. These results suggest that gut-residing microbes, including segmented filamentous bacteria, induce IL-17 production in GALT and complement activation via the alternative complement pathway, which cause the host to be more susceptible to autoantibody-mediated arthritis.
authors.affiliation: Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: Bo-Eun
authors.initials: BE
authors.lastname: Jin
authors.affiliation: Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: Eunkyeong
authors.initials: E
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: A Reum
authors.initials: AR
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.affiliation: Konkuk University Medical Center, Seoul 143-701, Korea.
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: Jeehee
authors.initials: J
authors.lastname: Youn
keywords: Antibiotics; Gut-residing microbes; IL-17; K/BxN serum-transferred arthritis; Segmented filamentous bacteria