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Fas Ligand-Mediated Exocrinopathy Resembling Sjögren’s Syndrome in Mice Transgenic for IL-10

1999; American Association of Immunologists; Volume: 162; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.162.5.2488

1550-6606

Ichiro Saito, Kumiko Haruta, Misa Shimuta, Hiroko Inoue, Hiroshi Sakurai, Koichi Yamada, Naozumi Ishimaru, Hiroyuki Higashiyama, Takayuki Sumida, Hiroshi Ishida, Takashi Suda, Tetsuo Noda, Yoshio Hayashi, Kazuo Tsubota,

Cell Adhesion Molecules Research

Abstract Although IL-10 has been implicated in the pathogenesis of several autoimmune diseases, the mechanisms by which this cytokine mediates inflammatory lesions remain to be elucidated. Exocrine gland destruction is an important early step in the development of Sjögren’s syndrome. To better understand the role of IL-10 in Sjögren’s syndrome, we made transgenic mice in which the mouse IL-10 gene was regulated by the human salivary amylase promoter. Transgenic expression of IL-10 induced apoptosis of glandular tissue destruction and lymphocyte infiltration consisting primarily of Fas-ligand (FasL)+ CD4+ T cells, as well as in vitro up-regulation of FasL expression on T cells. These data suggest that overexpression of IL-10 in the glands and their subsequent Fas/FasL-mediated bystander tissue destruction is a causal factor in the development of this disease.