title: Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behcet's disease.
abstract: We have reported that helper T type 17 (Th17) cells increased in patients with Behcet's disease (BD). It remains obscure how Th17 cells increase in the patients. We here analyzed whether T cells preferentially differentiate into Th17 cells in response to various inflammatory cytokines in patients with BD. Exogenous interleukin (IL)23 sustained the higher Th17 cell frequencies of CD4+CD45RO+ T cells after a 2-day culture in vitro in patients with BD, whereas the T cell subpopulation of normal individuals did not respond to IL23 to sustain/increase Th17 cell frequencies. IL23 receptor positive cell frequencies in freshly isolated BD CD4+CD45RO+ T cells correlated with Th17 cell frequencies assessed by intracellular cytokine staining. After a 2-day culture with IL23, BD CD4+ T cells retained the correlation between IL23 receptor expression level and extent of IL17 secretion (as indicated by Th17 cell frequencies), whereas such correlation was not noted in normal individuals. IL23 signals with its receptor were thus suggested to induce IL17 secretion (Th17 cell frequencies) in a short-time culture in patients with BD. We cultured CD4+CD45RO- T cells for 11 days with various inflammatory cytokines to study which cytokine associated with the enhanced Th17 frequencies in the patients. IL17 production by CD4+CD45RO- T cells of BD patients increased significantly by the supplementation of IL1β and tumor necrosis factor (TNF)α, in addition to IL23, compared with that of normal individuals. These results suggest that proinflammatory cytokines, such as IL1β, TNFα, and IL23, may associate with the expansion of Th17 cells in patients with BD. This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000003806).
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takai
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Takada
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Naruyoshi
authors.initials: N
authors.lastname: Fujiwara
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Nagisa
authors.initials: N
authors.lastname: Arimitsu
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Sueshige
authors.initials: S
authors.lastname: Wakisaka
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Immunology and Medicine, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan. n3suzuki@marianna-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D001528:Behcet Syndrome / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha
keywords: Behcet’s disease; IFNγ; IL17; IL23; IL23 receptor; Th17 cells