Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of scleroderma

Eur J Immunol. 1998 Sep;28(9):2619-29. doi: 10.1002/(SICI)1521-4141(199809)28:09<2619::AID-IMMU2619>3.0.CO;2-M.


The tight-skin (Tsk/+) mutant mouse, a putative murine model of scleroderma, is characterized primarily by the excessive deposition of collagen and other extracellular matrix molecules in the dermis, and also by a developmentally acquired defect in pulmonary architecture. Passive transfer experiments have suggested an etiologic role for the immune system in Tsk/+ dermal pathology. In addition, CD4+ T lymphocytes have been shown to be required for the excessive accumulation of dermal collagen in these mice. As IL-4, a product of differentiated CD4+ T cells, is capable of regulating the synthesis of various matrix molecules (including type I collagen) by fibroblasts in vitro, we investigated the potential role of IL-4 in mediating Tsk/+ dermal fibrosis. Confirming that Tsk/+ cells are capable of responding to IL-4, we found receptors for this cytokine on Tsk/+ embryonic fibroblasts and a dermal fibroblast cell line derived from these mice. Furthermore, IL-4 receptors on Tsk/+ fibroblasts were functional since IL-4 stimulation in vitro increased type I collagen secretion from these cells. These results demonstrated the potential for IL-4 to be directly involved in the excessive deposition of dermal collagen in Tsk/+ mice. Critical insight into the role played by IL-4 in mediating the dermal phenotype, however, was obtained following the administration of neutralizing anti-lL-4 antibodies to Tsk/+ mice. This treatment prevented the development of dermal fibrosis, leading to normalization of dermal collagen content. Given the requirement for CD4+ T cells in Tsk/+ dermal fibrosis, our results suggest that Th2 cells and/or factors elaborated by this T cell subset may play a key role in regulating dermal collagen content in this strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Collagen / antagonists & inhibitors
  • Collagen / metabolism*
  • Disease Models, Animal
  • Interleukin-4 / immunology*
  • Mice
  • Mice, Mutant Strains
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology*
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / metabolism*
  • Skin / immunology
  • Skin / metabolism
  • T-Lymphocytes / immunology*


  • Antibodies, Monoclonal
  • Interleukin-4
  • Collagen
  • Protein-Tyrosine Kinases
  • emt protein-tyrosine kinase