Overexpression of T-bet in T cells accelerates autoimmune glomerulonephritis in mice with a dominant Th1 background

被引:0
作者
Shimohata, Homare [1 ,2 ]
Yamada, Akiko [2 ]
Yoh, Keigyou [1 ]
Ishizaki, Kazusa [2 ]
Morito, Naoki [1 ]
Yamagata, Kunihiro [1 ]
Takahashi, Satoru [2 ]
机构
[1] Univ Tsukuba, Doctoral Program Clin Sci, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan
[2] Univ Tsukuba, Grad Sch Comprehens Human Sci, Doctoral Program Life Syst Med Sci, Dept Anat & Embryol, Tsukuba, Ibaraki 3058575, Japan
关键词
Autoimmunity; Mice; Th1; cells; Th2; Transcription factors; TRANSCRIPTION FACTOR GATA-3; LINEAGE COMMITMENT; GENE; EXPRESSION; LYMPHOCYTES; NEPHRITIS; DISEASES; THYMUS; CD4;
D O I
暂无
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: An imbalance of T helper 1 (Th1)/Th2 is thought to contribute to the pathogenesis of autoimmune diseases. The differentiation of T cells into Th1 or Th2 subtypes is under the regulation of several transcription factors. Among these, transcription factor T-bet has been demonstrated to play an important role in Th1 cell differentiation. Methods: To examine how Th1/Th2 imbalance affects the development of autoimmune disease, we overexpressed T-bet in the T lymphocytes of C57BL/6 x BXSB/MpJ-Yaa F1 (Yaa) mice. Results: Yaa mice developed autoimmune nephritis similarly to BXSB/MpJ-Yaa mice, which are commonly used as a model for the Th1-dominant murine lupus. T-bet overexpression in T cells aggravated the 50% mortality of T-bet transgenic Yaa mice relative to Yaa mice, and increased proteinuria, the severity of glomerulonephritis in T-bet transgenic Yaa mice. T-bet overexpression in Yaa mice led simultaneously to an elevated ratio of Th1/Th2 immunoglobulin (IgG2a/IgG1). Intracellular cytokine analysis showed that IL-4 and IL-5 was suppressed, and IFN-gamma was induced in stimulated T cells from the T-bet transgenic Yaa mice. Conclusions: These results indicate that T-bet stimulated the differentiation of Th1 cells and accelerated the disease severity in Yaa mice. These results suggest that Th1/Th2 imbalance contributes to the glomerulonephritis severity in Yaa mice, and Th1/Th2 transcriptional regulation is important for autoimmune glomerulonephritis.
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页码:123 / 129
页数:7
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