T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation

Karin L. Heckman, Suresh Radhakrishnan, Tobias Peikert, Koji Iijima, Hugh C. McGregor, Michael P. Bell, Hirohito Kita, Larry R. Pease

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

By cross-linking B7-DC on dendritic cells (DC) the human IgM antibody (B7-DC XAb) shifts polarized immune responses from Th2 to Th1 in an antigen-specific manner. The molecular determinants governing the ability of DC to reprogram the polarity of T cell recall responses are not yet known. In addition to the expected role of T-bet expressed by T cells in regulating Th1 responses, we find using in vitro assays and an established in vivo model of allergic airway inflammation that T-bet expression by DC is also required for the polarity shift promoted by B7-DC XAb. T-bet expression by both T cells and DC is critically important for B7-DC XAb-induced down-regulation of IL-4, up-regulation of IFN-γ and suppression of allergic airway inflammation. Moreover, retroviral reconstitution of T-bet expression in T-bet-deficient DC rescued their ability to modulate both naive and memory T-cell responses from Th2 to Th1. Our observations further our understanding of the critical mediators controlling the ability of DC to modify the responses of previously activated T cells and reveal the interesting use of the same transcription factor to regulate the inductive phenotype of DC and the inducible phenotype of T cells.

Original languageEnglish (US)
Pages (from-to)2464-2474
Number of pages11
JournalEuropean Journal of Immunology
Volume38
Issue number9
DOIs
StatePublished - Sep 2008

Keywords

  • Dendritic cells
  • Immune regulation
  • T-bet
  • T-box domain proteins
  • Transcription factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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