IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis

Matthew R. Macey, Jamie L. Sturgill, Johanna K. Morales, Yves T. Falanga, Joshua Morales, Sarah K. Norton, Nitin Yerram, Hoon Shim, Josephine Fernando, Alasdair M. Gifillan, Gregorio Gomez, Lawrence Schwartz, Carole Oskeritzian, Sarah Spiegel, Daniel Conrad, John J. Ryan

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.

Original languageEnglish
Pages (from-to)4688-4695
Number of pages8
JournalJournal of Immunology
Volume184
Issue number9
DOIs
StatePublished - May 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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