Interleukin‐21 and tumor necrosis factor‐α are critical for the development of autoimmune gastritis in mice

Abstract Background and Aim 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 Patients with AIG initially respond to corticosteroids but have a great potential to relapse after treatment is withdrawn.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.