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Interferon (IFN)-γ acts as a critical proinflammatory mediator in autoimmune processes, whereas it exerts regulatory functions to limit tissue damage associated with inflammation. However, a detailed understanding of the complex roles of IFN-γ in the development of organ-specific autoimmunity is still lacking. Recently, we found that programmed cell death 1-deficient mice thymectomized 3 days after birth (NTx-PD-1− / −  mice) concurrently developed autoimmune hepatitis (AIH) and autoimmune gastritis (AIG). In this study, we investigated the roles of IFN-γ in the development of AIH and AIG in this mouse model. In NTx-PD-1− / −  mice, serum levels of IFN-γ were markedly elevated. Neutralization of IFN-γ prevented the development of AIG. However, the same treatment exacerbated hepatic T-cell infiltration in AIH. Because of the loss of anti-proliferative effects by IFN-γ, neutralization of IFN-γ increased T-cell proliferation in the spleen and liver, resulting in exacerbated T-cell infiltration in the liver. On the other hand, in the development of AIG, CD4++ T-cell migration into the gastric mucosa is essential for induction. CCL20 expression was up-regulated in the gastric mucosa, and anti-CCL20 suppressed CD4++ T-cell infiltration into the gastric mucosa. Importantly, anti-IFN-γ suppressed CCL20 expression and infiltration of CD4++ T cells in the gastric mucosa, whereas in vivo injection of recombinant IFN-γ up-regulated CCL20 expression in the stomach, suggesting that IFN-γ is critically involved in CD4++ T-cell accumulation in AIG by up-regulating local CCL20 expression. In conclusion, IFN-γ is involved differently in the development of AIH and of AIG. IFN-γ negatively regulates T-cell proliferation in fatal AIH, whereas it initiates development of AIG. These findings imply that increased production of IFN-γ induced by an organ-specific autoimmunity may trigger the concurrent development of another organ-specific autoimmune disease. [ABSTRACT FROM AUTHOR]

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.