title: Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease.
abstract: Behçet's disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet's disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4(+) T cells from the peripheral blood of Behçet's disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti-TNF-α- and anti-IL-6-blocking Abs, Behçet's disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22-producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet's disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet's disease.
authors: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, Tokyo 113-8519, Japan. sunaoph@cdb.riken.jp
authors: Sunao
authors: S
authors: Sugita
authors: Yuko
authors: Y
authors: Kawazoe
authors: Ayano
authors: A
authors: Imai
authors: Tatsushi
authors: T
authors: Kawaguchi
authors: Shintaro
authors: S
authors: Horie
authors: Hiroshi
authors: H
authors: Keino
authors: Masayo
authors: M
authors: Takahashi
authors: Manabu
authors: M
authors: Mochizuki
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001528:Behcet Syndrome / Q000150:complications* / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D018121:Receptors, Cytokine / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D014605:Uveitis / Q000209:etiology*; D000097043:Interleukin-22
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007378:Interleukins; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22
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