title: Overexpression of T-bet in T cells accelerates autoimmune glomerulonephritis in mice with a dominant Th1 background.
abstract: 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/6xBXSB/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.
authors.affiliation: Department of Anatomy and Embryology, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Homare
authors.initials: H
authors.lastname: Shimohata
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Keigyou
authors.initials: K
authors.lastname: Yoh
authors.forename: Kazusa
authors.initials: K
authors.lastname: Ishizaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Morito
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology*; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012720:Severity of Illness Index; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology*; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology; D000098815:T-bet Transcription Factor
chemical_list: D007074:Immunoglobulin G; D015848:Interleukin-5; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma