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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Dendritic Cells
Inflammation
T-Lymphocytes
Phenotype
Interleukin-4
Immunoglobulin M
Transcription Factors
Up-Regulation
Down-Regulation
Antigens
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation. / Heckman, Karin L.; Radhakrishnan, Suresh; Peikert, Tobias D; Iijima, Koji; McGregor, Hugh C.; Bell, Michael P.; Kita, Hirohito; Pease, Larry R.

In: European Journal of Immunology, Vol. 38, No. 9, 09.2008, p. 2464-2474.

Research output: Contribution to journalArticle

Heckman, Karin L. ; Radhakrishnan, Suresh ; Peikert, Tobias D ; Iijima, Koji ; McGregor, Hugh C. ; Bell, Michael P. ; Kita, Hirohito ; Pease, Larry R. / T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation. In: European Journal of Immunology. 2008 ; Vol. 38, No. 9. pp. 2464-2474.
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