Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1

Hiroshi Ohnishi, Nobuaki Miyahara, Azzeddine Dakhama, Katsuyuki Takeda, Steven Mathis, Bodduluri Haribabu, Erwin W. Gelfand

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background: Leukotriene B4 (LTB4) is a potent inflammatory lipid mediator that binds to LTB4 receptor 1 (BLT1). Ligation of BLT1 by LTB4 plays an important role in the recruitment of effector memory CD8+ T cells into the airways of sensitized and challenged mice. Objectives: The effects of the corticosteroid dexamethasone (DEX) on BLT1-expressing effector memory CD8+ T cells and effector memory CD8+ T cell-mediated airway hyperresponsiveness (AHR) and allergic inflammation were determined. Methods: Effector memory CD8+ T cells were generated from ovalbumin257-264-primed mononuclear cells from OT-1 mice in the presence of IL-2. In some cultures DEX was added. The effects of DEX on BLT1 expression, LTB4-induced Ca2+ influx, phosphorylation of extracellular signal-regulated kinase 1/2, chemotaxis, and effector memory CD8+ T cell-mediated AHR were examined. Results: DEX-treated effector memory CD8+ T cells showed significant increases in surface expression of BLT1, LTB4-induced intracellular Ca2+ influx, phosphorylation of extracellular signal-regulated kinase 1/2, and chemotaxis. Upregulation of BLT1 by DEX was accompanied by increased IL-2 receptor expression. Adoptive transfer of DEX-treated effector memory CD8+ T cells into ovalbumin-sensitized and ovalbumin-challenged CD8-/- mice resulted in significant increases in AHR, allergic inflammation, goblet cell metaplasia, and numbers of both CD8+ and CD4+ T cells in the bronchoalveolar lavage fluid and lungs. Conclusions: Corticosteroids upregulate BLT1 on effector memory CD8+ T cells and related signaling pathways and potentiate allergic airway inflammation and AHR induced by these cells.

Original languageEnglish
Pages (from-to)864-871.e4
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

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Keywords

  • CD122
  • CD25
  • Central memory T cell
  • corticosteroid-insensitive asthma
  • effector memory T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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