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CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis.
Zhen-lin Zhang1, Bo Lin, Lu-yang Yu
1Center for Preventing and Treating Osteoporosis, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China. ZZL2002@madmail.com.cn
Chinese Medical Journal
|August 16, 2005
Summary
Fas ligand (FasL) expression in transgenic mice reduced autoimmune thyroiditis severity. This indicates FasL plays a key role in inhibiting thyroid lymphocytic infiltration and improving experimental autoimmune thyroiditis (EAT).
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- The role of Fas ligand (FasL) in autoimmune thyroiditis pathogenesis is inconsistent.
- This study investigates the effects of FasL on experimental autoimmune thyroiditis (EAT) using transgenic mice.
Purpose of the Study:
- To investigate the effects of FasL on the pathogenesis of EAT.
- To determine if ubiquitous expression of human FasL (hFasL) in transgenic mice can ameliorate EAT.
Main Methods:
- CMV-hFasL transgenic mice were used as an EAT model by injecting porcine thyroglobulin (pTg).
- hFasL expression and activity were confirmed via RT-PCR, Western blot, and cell-killing assays.
- Lymphocytic infiltration, spleen lymphocyte populations (CD4+, CD8+), and serum IFN-gamma levels were assessed.
Main Results:
- hFasL expression was confirmed in transgenic mice thyroids.
- Thyroid cells from transgenic mice induced significantly higher apoptosis in Jurket cells compared to wild-type.
- Transgenic mice showed significantly reduced lymphocytic infiltration in thyroids, decreased spleen lymphocytes, and lower serum IFN-gamma levels post-immunization.
Conclusions:
- FasL plays a significant role in the pathogenesis of autoimmune thyroiditis.
- Ubiquitous hFasL expression in transgenic mice inhibits thyroid lymphocytic infiltration in EAT.
- Transgenic hFasL ameliorates the course of experimental autoimmune thyroiditis.