Tissue-specific expression of interleukin-4 induces extracellular matrix accumulation and extravasation of B cells

Regula Mueller, Troy Krahl, Nora Sarvetnick

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We have assessed the consequences of tissue-specific production of IL-4 by generating transgenic mice that express IL-4 under the control of the human insulin promoter in the Langerhans' islets of the pancreas. In these transgenic mice, designated Ins-IL-4 mice, we observed the deposition of extracellular matrix (ECM) around the islets beginning at an early age. This matrix was interspersed with eosinophils, macrophages, and fibroblasts; T cells were notably absent. AS the mice aged, the exocrine tissue was steadily replaced by ECM and adipose tissue, and the pancreatic islets were disrupted by ECM deposition and newly formed pancreatic ducts. Most striking was the preferential accumulation of B lymphocytes around the blood vessels close to the islets. Vascular changes included induction of MadCAM (mucosal addressin cell adhesion molecule)-1, von Willebrand factor, and intercellular adhesion molecule-1 on endothelial cells in panereata of Ins-IL-4 mice. Overall, tissue-specific expression of IL-4 induced a complex, localized host response that resulted in the excessive generation of ECM and the selective recruitment of inflammatory cells. These findings suggest that IL-4 has a role in (a) the regulation of potentially pathologic fibrotic events associated with chronic inflammatory lesions and (b) the recruitment of inflammatory cells in Th2 cell-dependent diseases such as allergic disorders.

Original languageEnglish (US)
Pages (from-to)117-128
Number of pages12
JournalLaboratory Investigation
Volume76
Issue number1
Publication statusPublished - Jan 1 1997

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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