A role for T helper 2 cells in mediating skin fibrosis in tight-skin mice

Cell Immunol. 1999 Aug 25;196(1):60-8. doi: 10.1006/cimm.1999.1537.


Mice heterozygous for the tight-skin (Tsk) mutation develop skin fibrosis. Previous studies have implicated a role for the immune system and, specifically, CD4(+) T cells, in the etiology of skin fibrosis in Tsk/+ mice. We have recently shown that the administration of neutralizing anti-IL-4 antibodies to Tsk/+ mice prevented the development of skin fibrosis in these mice. Since IL-4 is a major cytokine produced by T helper 2 (Th2) cells, we investigated the role of Th2 cells in mediating skin fibrosis in Tsk/+ mice. Previous studies have shown that the development of Th2 cells in non-Tsk mice is abrogated in mice with null mutation for either the IL-4 or the Stat6 gene. In this study we showed that the polarization of CD4(+) T cells from Tsk/+ mice toward the Th2 lineage is also dependent on a functioning IL-4 or Stat6 gene. More importantly, the development of skin fibrosis in Tsk/+ mice was abrogated by the IL4(-/-) or the Stat6(-/-) mutation. We also determined whether alteration of the TCR repertoire in Tsk/+ mice, achieved by the introduction of TCR transgenes, was able to prevent the development of skin fibrosis in Tsk/+ mice. We found that the exclusive usage of the Vbeta8.2 gene segment by T cells was sufficient to prevent skin fibrosis in Tsk/+ mice. This result suggests that the exclusive use of this Vbeta gene segment by T cells may have prevented the development of fibrosis-causing Th2 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Fibrosis / immunology
  • Fibrosis / pathology
  • H-2 Antigens / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • STAT6 Transcription Factor
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / immunology


  • H-2 Antigens
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • T-cell receptor Vbeta 8.2
  • Trans-Activators
  • Interleukin-4
  • Interferon-gamma