title: Interleukin-21 and tumor necrosis factor-α are critical for the development of autoimmune gastritis in mice.
abstract: OBJECTIVE
  Autoimmune gastritis (AIG), an organ-specific autoimmune disease, is accompanied by achlorhydria, pernicious anemia, gastric carcinoid tumors, and gastric cancer. Patients with AIG initially respond to corticosteroids but have a great potential to relapse after treatment is withdrawn. This study examines the roles of cytokines in order to identify potential therapeutic options for AIG patients.
  
  
  METHODS
  Using a mouse model of AIG, we monitored disease progression and administered antibodies in vivo to block cytokines.
  
  
  RESULTS
  We developed a mouse model of AIG with early onset and rapid progression in which neonatal thymectomy (NTx) was performed on programmed cell death 1-deficient (PD-1(-/-) ) mice on the BALB/c background. Using NTx-PD-1(-/-) mice, we found that in AIG lesions, interferon-γ, and tumor necrosis factor (TNF)-α together with interleukin-21 (IL-21) were highly expressed in the inflamed gastric mucosa. In addition, as with the injection of dexamethasone, in vivo administration of either anti-TNF-α or anti-IL-21 suppressed the development of AIG in NTx-PD-1(-/-) mice.
  
  
  CONCLUSIONS
  These data reveal the essential role of IL-21 in the development of AIG and suggest that in addition to corticosteroids, anti-TNF-α as well as anti-IL-21 have the potential to induce the remission of AIG, offering additional therapeutic options for AIG patients.
authors: Department of Gastroenterology and Hepatology, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Hisayo
authors: H
authors: Nishiura
authors: Satoru
authors: S
authors: Iwamoto
authors: Masahiro
authors: M
authors: Kido
authors: Nobuhiro
authors: N
authors: Aoki
authors: Ryutaro
authors: R
authors: Maruoka
authors: Aki
authors: A
authors: Ikeda
authors: Tsutomu
authors: T
authors: Chiba
authors: Norihiko
authors: N
authors: Watanabe
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D005756:Gastritis / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000098546:Interleukin-21