%0 Journal Article
%T Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Beh£¿et's disease
%A Sunao Sugita
%A Yuko Kawazoe
%A Ayano Imai
%A Yukiko Yamada
%A Shintaro Horie
%A Manabu Mochizuki
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3824
%X To measure inflammatory cytokines, ocular fluid samples from BD patients being treated with infliximab were collected. Cluster of differentiation 4 (CD4)+ T cells from BD patients with active uveitis were co-cultured with anti-cluster of differentiation 3/cluster of differentiation 28 (CD3/CD28) antibodies in the presence of infliximab. For the induction of Th17 cells, CD4+ T cells from BD patients were co-cultured with anti-CD3/CD28, anti-interferon-gamma (anti-IFN-¦Ã), anti-interleukin-4 (anti-IL-4), and recombinant proteins such as interleukin-1 beta (IL-1¦Â), interleukin-6 (IL-6), interleukin-23 (IL-23), and TNF-¦Á. The BD T cells were co-cultured with infliximab, and the production of interleukin-17 (IL-17) was evaluated by ELISA and flow cytometry, and the expression of retinoid-acid receptor-related orphan receptor gamma t (ROR¦Ãt) was also evaluated by flow cytometry. In addition, intraocular cells collected from mice with experimental autoimmune uveitis (EAU) were used for the assay with anti-TNF-¦Á blocking antibody.Ocular fluids from active uveitis patients who have BD contained significant amounts of inflammatory cytokines such as IFN-¦Ã, IL-2, TNF-¦Á, IL-6, and IL-17, while ocular fluids from infliximab patients did not contain any inflammatory cytokines. Activated CD4+ T cells from BD patients produced large amounts of TNF-¦Á and IL-17, whereas T cells in the presence of infliximab failed to produce these cytokines. Polarized Th17 cell lines from BD patients produced large amounts of IL-17, and Th17 cells exposed to infliximab had significantly reduced IL-17 production. Polarized BD Th17 cells expressed large amounts of transcription factor ROR¦Ãt. In contrast, in vitro-treated infliximab Th17 cells expressed less ROR¦Ãt. Moreover, intraocular T cells from EAU mice had a high population of IL-17+ cells, and retinal antigen-specific T cells from EAU mice produced large amounts of IL-17 in the presence of retinal peptide. However, the EAU T cells produced less IL-
%U http://arthritis-research.com/content/14/3/R99