Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA

Immunobiology. 2016 Apr;221(4):577-85. doi: 10.1016/j.imbio.2015.12.001. Epub 2015 Dec 15.


We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer's patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer's patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli.

Keywords: GATA-3; IgA deposition; IgA nephropathy; Mucosal immunity; Th1/Th2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cell Proliferation
  • Cholera Toxin / administration & dosage
  • Cholera Toxin / immunology*
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Gene Expression
  • Glomerulonephritis, IGA / chemically induced
  • Glomerulonephritis, IGA / genetics
  • Glomerulonephritis, IGA / immunology*
  • Glomerulonephritis, IGA / pathology
  • Immune Tolerance
  • Immunization
  • Immunoglobulin A / biosynthesis*
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology*
  • Mannose-Binding Lectin / genetics
  • Mannose-Binding Lectin / immunology
  • Mesangial Cells / drug effects
  • Mesangial Cells / immunology
  • Mesangial Cells / pathology
  • Mice
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peyer's Patches / drug effects
  • Peyer's Patches / immunology*
  • Peyer's Patches / pathology
  • Primary Cell Culture
  • Spleen / drug effects
  • Spleen / immunology*
  • Spleen / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / pathology


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Immunoglobulin A
  • Interleukin-5
  • Mannose-Binding Lectin
  • Ovalbumin
  • Cholera Toxin