IL-4 induces differentiation of human embryonic stem cells into fibrogenic fibroblast-like cells

Tadashi Sato, Xiang-de Liu, Hesham E Basma, Shinsaku Togo, Hisatoshi Sugiura, Amy Nelson, Masanori Nakanishi, Nobuhiro Kanaji, Xingqi Wang, Miok Kim, Yingji Li, Joel Michalski, Maha Farid, John G Sharp, Stephen I. Rennard

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background: Fibroblast heterogeneity is recognized, and fibroblasts from diseased tissues, including those of asthmatic subjects, have functional phenotypes that differ from normal tissue. However, progenitor-progeny relationships and the factors that control fibroblast differentiation are poorly defined. Objective: We sought to determine whether IL-4 could alter the functional phenotype of fibroblasts during their differentiation from stem/progenitor cells. Methods: Using a 3-dimensional collagen gel system, we obtained embryoid bodies derived from human embryonic stem cells and recovered spindle-shaped cells consistent with fibroblasts that had differentiated in the presence or absence of IL-4. Results: IL-4-induced fibroblast-like cells were more active in contraction of collagen gels, migration, and production of fibronectin than control (without IL-4) cells. IL-4-induced cells demonstrated less expression of miR-155, which modulated contraction, migration, and fibronectin production. These differences persisted in culture without further addition of IL-4, suggesting the differentiated phenotype might be a permanent alteration. Conclusion: The current study demonstrates that IL-4 induces differentiation of stem/precursor cells into fibroblast-like cells that demonstrate a more fibrogenic phenotype, which is due to reduced expression of miR-155. These findings provide a novel mechanism for the persistent abnormalities in IL-4-related diseases and a novel target to regulate tissue remodeling by fibroblasts.

Original languageEnglish (US)
Pages (from-to)1595-1603.e9
JournalJournal of Allergy and Clinical Immunology
Volume127
Issue number6
DOIs
Publication statusPublished - Jun 2011

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Keywords

  • Embryonic stem cells, fibroblasts, IL-4, fibrosis, asthma, microRNA
  • miR-155, chemotaxis, collagen gel contraction, TGF-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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