title: NFKBIL1 confers resistance to experimental autoimmune arthritis through the regulation of dendritic cell functions.
abstract: We and others have reported that human NF-κB inhibitor-like-1 (NFKBIL1) was a putative susceptible gene for autoimmune diseases such as rheumatoid arthritis (RA). However, its precise role in the pathogenesis of RA is still largely unknown. In this study, we generated transgenic mice expressing human NFKBIL1 (NFKBIL1-Tg) and examined whether NFKBIL1 plays some role(s) in the development of autoimmune arthritis. In both a collagen-induced arthritis model and a collagen antibody-induced arthritis model, NFKBIL1-Tg mice showed resistance to arthritis compared to control mice, indicating that the gene product of NFKBIL1 was involved in the control of thusly induced arthritis. Total spleen cells of NFKBIL1-Tg mouse showed decreased proliferation to mitogenic stimuli, consistent with its resistance to arthritis. Unexpectedly, purified T cells of NFKBIL1-Tg mouse showed increased proliferation and cytokine production. This apparent discrepancy was accounted for by the impaired functions of antigen-presenting cells of NFKBIL1-Tg mouse; both T/B cell-depleted spleen cells and bone marrow-derived dendritic cells of the Tg mouse induced less prominent proliferation and IL-2 production of T cells. Furthermore, dendritic cells (DCs) derived from NFKBIL1-Tg mouse showed lower expression of co-stimulatory molecules and decreased production of inflammatory cytokines when they were activated by lipopolysaccharide. Taken together, these results indicated that NFKBIL1 affected the pathogenesis of RA at least in part through the regulation of DC functions.
authors.affiliation: Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Chiba
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzaka
authors.forename: T
authors.initials: T
authors.lastname: Warita
authors.forename: T
authors.initials: T
authors.lastname: Sugoh
authors.forename: K
authors.initials: K
authors.lastname: Miyashita
authors.forename: A
authors.initials: A
authors.lastname: Tajima
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Inoko
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Kimura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D004268:DNA-Binding Proteins; C518886:Nfkbil1 protein, mouse; D014157:Transcription Factors