This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fang, Y. Articles by Braley-Mullen, H. Search for Related Content PubMed Articles by Fang, Y. Articles by Braley-Mullen, H.

(American Journal of Pathology. 2007;170:875-887.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060816

Murine FLIP Transgene Expressed on Thyroid Epithelial Cells Promotes Resolution of Granulomatous Experimental Autoimmune Thyroiditis in DBA/1 Mice

Yujiang Fang^*, Yongzhong Wei^*, Vincent DeMarco, Kemin Chen^*, Gordon C. Sharp^* and Helen Braley-Mullen^*

From the Departments of Internal Medicine,^* Child Health, Pathology, Molecular Microbiology and Immunology, University of Missouri School of Medicine, and Veterans Affairs Research Service, Columbia, Missouri

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin-sensitized splenocytes activated in vitro with mouse thyroglobulin and interleukin-12. In wild-type (WT) DBA/1 recipients of WT donor splenocytes, thyroid lesions reach maximal severity at day 20, with ongoing inflammation and extensive fibrosis at day 60. Our previous studies indicated the site of expression of FLIP and Fas ligand [thyroid epithelial cells (TECs) versus inflammatory cells] differed in mice when lesions would resolve or progress to fibrosis. To test the hypothesis that expression of FLIP by TECs would promote earlier G-EAT resolution in DBA/1 mice, transgenic (Tg) DBA/1 mice expressing FLIP on TECs were generated. In FLIP Tg⁺ and Tg^– littermate recipients of WT donor splenocytes, G-EAT severity was comparable at day 20, but fibrosis was decreased, and many lesions resolved by day 60 in Tg⁺ but not Tg^– recipients. FLIP and Fas ligand were primarily expressed by TECs in Tg⁺ recipients and by inflammatory cells in Tg^– recipients at day 60. Apoptosis of inflammatory cells was greater, and expression of proinflammatory cytokines was decreased in thyroids of Tg⁺ compared with Tg^– recipients. These results are consistent with the hypothesis that transgenic expression of FLIP on thyroid epithelial cells promotes earlier resolution of granulomatous experimental autoimmune thyroiditis.

This article has been cited by other articles:

				S. Yu, G. C. Sharp, and H. Braley-Mullen TGF-{beta} Promotes Thyroid Epithelial Cell Hyperplasia and Fibrosis in IFN-{gamma}-Deficient NOD.H-2h4 Mice J. Immunol., August 1, 2008; 181(3): 2238 - 2245. [Abstract] [Full Text] [PDF]

				Y. Fang and H. Braley-Mullen Cultured Murine Thyroid Epithelial Cells Expressing Transgenic Fas-Associated Death Domain-Like Interleukin-1{beta} Converting Enzyme Inhibitory Protein Are Protected from Fas-Mediated Apoptosis Endocrinology, July 1, 2008; 149(7): 3321 - 3329. [Abstract] [Full Text] [PDF]

				Y. Fang, V. G. DeMarco, G. C. Sharp, and H. Braley-Mullen Expression of Transgenic FLIP on Thyroid Epithelial Cells Inhibits Induction and Promotes Resolution of Granulomatous Experimental Autoimmune Thyroiditis in CBA/J Mice Endocrinology, December 1, 2007; 148(12): 5734 - 5745. [Abstract] [Full Text] [PDF]