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

36 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
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Fingerprint

Leukotriene B4 Receptors
Adrenal Cortex Hormones
Inflammation
T-Lymphocytes
Dexamethasone
Leukotriene B4
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Ovalbumin
Chemotaxis
Up-Regulation
Phosphorylation
Goblet Cells
Adoptive Transfer
Interleukin-2 Receptors
Bronchoalveolar Lavage Fluid
Metaplasia
Interleukin-2
Ligation
Cell Count

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1. / Ohnishi, Hiroshi; Miyahara, Nobuaki; Dakhama, Azzeddine; Takeda, Katsuyuki; Mathis, Steven; Haribabu, Bodduluri; Gelfand, Erwin W.

In: Journal of Allergy and Clinical Immunology, Vol. 121, No. 4, 04.2008.

Research output: Contribution to journalArticle

Ohnishi, Hiroshi ; Miyahara, Nobuaki ; Dakhama, Azzeddine ; Takeda, Katsuyuki ; Mathis, Steven ; Haribabu, Bodduluri ; Gelfand, Erwin W. / Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1. In: Journal of Allergy and Clinical Immunology. 2008 ; Vol. 121, No. 4.
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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.",
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T1 - Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1

AU - Ohnishi, Hiroshi

AU - Miyahara, Nobuaki

AU - Dakhama, Azzeddine

AU - Takeda, Katsuyuki

AU - Mathis, Steven

AU - Haribabu, Bodduluri

AU - Gelfand, Erwin W.

PY - 2008/4

Y1 - 2008/4

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AB - 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.

KW - CD122

KW - CD25

KW - Central memory T cell

KW - corticosteroid-insensitive asthma

KW - effector memory T cell

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