Transgenic overexpression of GATA-3 in T lymphocytes improves autoimmune glomerulonephritis in mice with a BXSB/MpJ-Yaa genetic background

Keigyou Yoh, Kazuko Shibuya, Naoki Morito, Takako Nakano, Kazusa Ishizaki, Homare Shimohata, Masato Nose, Shozo Izui, Akira Shibuya, Akio Koyama, James Douglas Engel, Masayuki Yamamoto, Satoru Takahashi

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32 Citations (Scopus)

Abstract

A T helper 1 (Th1)/Th2 imbalance 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 GATA-3 is thought to play an indispensable role in the development of T cells and the differentiation of Th2 cells. To examine how a Th1/Th2 imbalance affects the development of autoimmune disease, GATA-3 was overexpressed in the T lymphocytes of C57BL/6 × BXSB/MpJ-Yaa F 1 (Yaa) mice. Yaa mice developed autoimmune nephritis similarly to BXSB/MpJ-Yaa mice, which are commonly used as a model for Th1-dominant murine lupus. GATA-3 overexpression in T cells improved the 50% mortality incidence time for GATA-3-transgenic Yaa mice (41.6 wk), compared with Yaa mice (30.9 wk), and reduced proteinuria, serum creatinine levels, and the severity of glomerulonephritis in GATA-3-transgenic Yaa mice. GATA-3 overexpression in Yaa mice led to simultaneously elevated Th2 Ig (IgG1) and decreased Th1 Ig (IgG2a and IgG3) production and serum IFN-γ levels. Although IL-4 production remained unchanged, intracellular cytokine analyses demonstrated that IL-5 was induced and IFN-γ was suppressed in stimulated T cells from the GATA-3-transgenic Yaa mice. These results indicated that abundant GATA-3 was unable to stimulate complete differentiation of Th2 cells but did counteract the dominance of Th1 cells and alleviated the disease severity in Yaa mice. These data suggest that transcriptional regulation therapy may have potential as an effective strategy for treating autoimmune glomerulonephritis.

Original languageEnglish
Pages (from-to)2494-2502
Number of pages9
JournalJournal of the American Society of Nephrology
Volume14
Issue number10
DOIs
Publication statusPublished - 2003 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Yoh, K., Shibuya, K., Morito, N., Nakano, T., Ishizaki, K., Shimohata, H., Nose, M., Izui, S., Shibuya, A., Koyama, A., Engel, J. D., Yamamoto, M., & Takahashi, S. (2003). Transgenic overexpression of GATA-3 in T lymphocytes improves autoimmune glomerulonephritis in mice with a BXSB/MpJ-Yaa genetic background. Journal of the American Society of Nephrology, 14(10), 2494-2502. https://doi.org/10.1097/01.ASN.0000086473.23379.25