Fas ligand-mediated exocrinopathy resembling Sjogren's syndrome in mice transgenic for IL-10

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

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88 Citations (Scopus)

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 Sjogren's syndrome. To better understand the role of IL-10 in Sjogren'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 upregulation 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.

Original languageEnglish
Pages (from-to)2488-2494
Number of pages7
JournalJournal of Immunology
Volume162
Issue number5
Publication statusPublished - 1999 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Saito, I., Haruta, K., Shimuta, M., Inoue, H., Sakurai, H., Yamada, K., Ishimaru, N., Higashiyama, H., Sumida, T., Ishida, H., Suda, T., Noda, T., Hayashi, Y., & Tsubota, K. (1999). Fas ligand-mediated exocrinopathy resembling Sjogren's syndrome in mice transgenic for IL-10. Journal of Immunology, 162(5), 2488-2494.