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

Abstract：

: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.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Ong C,Wong C,Roberts CR,Teh HS,Jirik FR

doi

10.1002/(SICI)1521-4141(199809)28:09<2619::AID-IMM

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

2619-29

issue

eissn

0014-2980

issn

1521-4141

pii

10.1002/(SICI)1521-4141(199809)28:09<2619::AID-IMM

journal_volume

pub_type

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